CN112604051B - Total-liver type bioartificial liver system - Google Patents

Total-liver type bioartificial liver system Download PDF

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CN112604051B
CN112604051B CN202011416329.8A CN202011416329A CN112604051B CN 112604051 B CN112604051 B CN 112604051B CN 202011416329 A CN202011416329 A CN 202011416329A CN 112604051 B CN112604051 B CN 112604051B
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blood
liver
plasma
pipeline
storage tank
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CN112604051A (en
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高毅
薛巍松
李阳
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Guangdong Qianhui Biotechnology Co ltd
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Guangdong Qianhui Biotechnology Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3621Extra-corporeal blood circuits
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3621Extra-corporeal blood circuits
    • A61M1/3639Blood pressure control, pressure transducers specially adapted therefor
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/369Temperature treatment

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Abstract

The application provides a total-liver bioartificial liver system, which comprises a plasma separation circulation path, a liver perfusion circulation path, a plasma separation feedback circulation path and a blood storage tank which are relatively independent, wherein the blood storage tank is used for mixing plasma of a patient and an in-vitro liver oxygen carrier; the plasma separation circulation passage comprises a blood input pipeline, a first plasma separation pipeline and a blood return pipeline, and the first plasma separation pipeline is connected with the blood storage tank; the liver perfusion circulation passage comprises a biochemical purification pipeline provided with a total liver perfusion component, and the biochemical purification pipeline is connected with the blood storage tank; the plasma separation and return circulation passage comprises a second plasma separation and return circulation pipeline, the input end of the second plasma separation and return circulation pipeline is connected with the output end of the blood storage tank, and the return pipeline is connected between the second plasma separation and return circulation pipeline and the blood return pipeline. This application can adjust the perfusion pressure, flow and the velocity of flow of external liver better through setting up the blood storage tank, improves the efficiency of filling, shortens the cycle time.

Description

Total-liver type bioartificial liver system
Technical Field
The application relates to the fields of biology and medical equipment, in particular to a total-liver bioartificial liver system.
Background
An Artificial Liver Support System (ALSS) is a Liver replacement therapy method, which is based on the fact that the Liver has strong self-regeneration and repair capability, removes harmful substances, supplements substances necessary for human body, improves the internal environment of a patient, temporarily replaces partial functions of the Liver, creates conditions for repairing and regenerating Liver cells of a Liver failure patient, and creates time for waiting for a Liver transplantation donor by introducing an in-vitro mechanical, physicochemical or biological device. The current artificial liver is mainly divided into two main categories, namely, non-biological artificial liver using mechanical and physical and chemical devices and biological artificial liver containing cells or whole liver and other biological devices.
The biological artificial liver is an artificial liver system with a biological device as a core, and is usually a cell type biological artificial liver, but the cell type biological artificial liver takes free cells as a biological reaction device, and functions of metabolism, transformation, detoxification, synthesis and the like are performed by depending on biological functions of a certain number of single cells, so that the effect of treating patients with liver failure is achieved. However, compared with the natural in vivo liver, the cell type bioartificial liver has certain differences in cell number, three-dimensional structure, internal and external environment, and the current bioartificial liver has low flow rate, so that the current bioartificial liver is difficult to meet the requirements of patients.
Disclosure of Invention
The purpose of the application is to provide a total-liver bioartificial liver system with a wide circulation flow regulation range.
In order to achieve the above object, the present application provides the following technical solutions:
a total liver type biological artificial liver system comprises a plasma separation circulation path, a liver perfusion circulation path, a plasma separation feedback circulation path and a blood storage tank which are relatively independent, wherein the blood storage tank is used for mixing plasma input through the plasma separation circulation path and an extracorporeal liver oxygen carrier;
the plasma separation circulation passage comprises a blood input pipeline, a first plasma separation pipeline and a blood return pipeline, and the first plasma separation pipeline is connected with the input end of the blood storage tank;
the liver perfusion circulation passage comprises a biochemical purification pipeline, the biochemical purification pipeline is provided with a total liver perfusion component, the input end of the biochemical purification pipeline is connected with the output end of the blood storage tank, and the output end of the biochemical purification pipeline is connected with the input end of the blood storage tank;
the plasma separation and return circulation passage comprises a second plasma distribution circulation pipeline and a plasma return pipeline, the input end of the second plasma distribution circulation pipeline is connected with the output end of the blood storage tank, and the plasma return pipeline is connected between the second plasma distribution circulation pipeline and the blood return pipeline.
Further setting: first branch plasm way is including being equipped with the first blood separator of first blood entry, first plasma export, first blood cell export, and follow first plasma export is connected to the branch plasm branch road of blood storage tank, be equipped with the branch milk pump on the branch milk branch road.
Further setting: the blood input pipeline is connected with the first blood inlet, and a blood pumping pump is arranged on the blood input pipeline;
the blood return line is connected with the first blood cell outlet.
Further setting: the biochemical purification pipeline comprises a circulation branch connected with the input end and the output end of the blood storage tank, the total liver perfusion component is arranged on the circulation branch, and a peristaltic pump and an oxygenator are arranged on the circulation branch close to the output end of the blood storage tank.
Further setting: the whole liver perfusion assembly comprises a whole liver and a perfusion cabin body for accommodating the whole liver
Further setting: the whole liver is derived from animal liver.
Further setting: the whole liver is connected with a bile recovery device for recovering bile.
Further setting: the second divides the plasma circulation pipeline including the second plasma separator that is equipped with second blood entry, second plasma export and second blood cell export, second blood entry with the output of blood storage tank is connected and is equipped with the transfer pump between the two, the second blood cell export pass through the pipe with the input of blood storage tank is connected.
Further setting: the plasma return pipeline is connected with the second plasma outlet, a plasma return pump is arranged on the plasma return pipeline, a vein kettle is arranged on the blood return pipeline, and the plasma return pipeline is connected to the vein kettle.
Further setting: the output end of the blood storage tank, the liver perfusion circulation passage and the plasma separation and feedback circulation passage are connected through a three-way valve.
Compared with the prior art, the scheme of the application has the following advantages:
1. in the total-liver bioartificial liver system, the plasma of a patient separated by the plasma separation circulation passage connected with the patient is conveyed into the blood storage tank, and is oxygenated by the oxygenator with an extracorporeal liver oxygen carrier in the blood storage tank, and then enters the extracorporeal liver circulation passage for biological purification, and the extracorporeal liver circulation is divided into the liver perfusion circulation passage and the plasma separation feedback circulation passage, so that the perfusion pressure, the flow and the flow rate of the extracorporeal liver can be better regulated, the extracorporeal liver is ensured to be in the optimal internal and external environment, the extracorporeal liver can be well exerted, the synchronous circulation of the plasma separation circulation passage and the extracorporeal liver circulation passage can be realized by utilizing the blood storage tank, the perfusion efficiency is greatly improved, the circulation time is shortened, the blood purification efficiency is improved, and the liver self-regeneration opportunity is provided for the patient.
2. In the total-liver bioartificial liver system, the plasma separation and feedback circulation passage is arranged to separate the purified plasma from the in-vitro liver oxygen carrier and then feed the separated plasma back to the patient, so that the in-vitro liver oxygen carrier can be removed from the purified plasma, and the load on the heart is avoided; meanwhile, the in vitro liver oxygen carrier is returned to the blood storage tank for recycling, so that the utilization rate of the in vitro liver oxygen carrier is improved, and the cost is reduced.
Additional aspects and advantages of the present application will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the present application.
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The foregoing and/or additional aspects and advantages of the present application will become apparent and readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings of which:
FIG. 1 is a schematic structural diagram of one embodiment of a total liver bioartificial liver system of the present application;
FIG. 2a is a graph showing the relationship between blood ammonia time and the time of control group in the present application;
FIG. 2b is a graph showing the time-dependent changes in lactic acid between the experimental group and the control group in the present application;
FIG. 2c is a graph showing the time-varying relationship between total bilirubin in the experimental group and that in the control group;
FIG. 2d is a graph showing the direct bilirubin time dependence of the experimental group and the control group in the present application.
In the figure, 1, the plasma separation circulation path; 11. a first slurry separation pipeline; 111. a first plasma separator; 111-1, a first blood inlet; 111-2, a first plasma outlet; 111-3, a first blood cell outlet; 12. a blood input line; 121. a blood pump is pumped; 122. a drug input device; 123. the arteria cruris; 13. a blood return line; 131. a venous pot; 14. a pulp separation branch; 141. a slurry distributing pump; 2. a liver perfusion circulation path; 21. a whole liver perfusion assembly; 211. the whole liver; 212. filling the cabin; 213. a bile recovery device; 221. the anterior hepatic circulation branch; 222. the posthepatic circulation branch; 23. a peristaltic pump; 24. an oxygenator; 3. a plasma separation return circulation path; 31. a second plasma separator; 31-1, a second blood inlet; 31-2, a second plasma outlet; 31-3, a second blood cell outlet; 311. a conduit; 32. an infusion pump; 33. a slurry return pipeline; 331. a slurry return pump; 4. a blood storage tank; 41. three-way valve.
Detailed Description
Reference will now be made in detail to embodiments of the present application, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to the same or similar elements or elements having the same or similar function throughout. The embodiments described below with reference to the drawings are exemplary only for the purpose of explaining the present application and are not to be construed as limiting the present application.
Referring to fig. 1, the present application relates to a total liver type bioartificial liver system, which solves the problems that the circulation flow of the existing bioartificial liver system is low and the requirements of patients with severe liver failure are difficult to meet, can better regulate the perfusion pressure, flow and flow rate of the in vitro liver, and ensure that the in vitro liver is in the optimal internal and external environment, so that the system can perform good circulation purification and replacement functions.
The utility model provides a biological artificial liver system of total liver type includes plasma separation circulating line 1, external liver circulation route and blood storage tank 4, plasma separation circulating line 1 with external liver circulation route constitutes parallel circulation route through blood storage tank 4, external liver circulation route can divide again for liver perfusion circulating line 2 and plasma separation feedback circulating line 3, and wherein, blood storage tank 4 is used for mixing the warp patient plasma and the external liver oxygen carrier of 1 input of plasma separation circulating line to make patient plasma and the external liver oxygen carrier after mixing get into external liver circulation route. Among the external liver circulation route liver perfusion circulation route 2 be used for with patient's plasma and external liver oxygen carrier after mixing in the blood storage tank 4 carry out biological purification to realize the detoxification, the metabolism function to patient's plasma, patient's plasma and external liver oxygen carrier after purifying circulate back again in the blood storage tank 4, the rethread patient's plasma and external liver oxygen carrier after will detoxify separation of plasma feedback circulation route to patient's plasma and external liver oxygen carrier after will detoxify is reinfused back to the patient internal, in order to play the effect of purifying patient's blood better. The three passages of the plasma separation circulating passage 1, the liver perfusion circulating passage 2 and the plasma separation return circulating passage 3 are connected through the blood storage tank 4 and are relatively independent.
The extracorporeal liver oxygen carrier comprises red blood cells or artificial blood, and the blood storage tank 4 is provided with a joint (not shown) for inputting the extracorporeal liver oxygen carrier into the blood storage tank 4. The in vitro liver oxygen carrier can replace hemoglobin for conveying oxygen in human blood, and has the functions of carrying and supplying oxygen. This application avoids blood and the immunoreaction that external liver direct contact leads to through introducing external liver oxygen carrier and replacing human whole blood, red blood cell to fully ensure patient's safety, and the output of blood storage tank is equipped with oxygenator 24, with the abundant oxygenation of ensureing patient's plasma and external liver oxygen carrier, and provide oxygen for external liver oxygen carrier.
The plasma is separated by the plasma separation and circulation path 1, specifically, the plasma separation and circulation path 1 includes a first plasma separation line 11, a blood input line 12 and a blood return line 13, and the first plasma separation line 11 is connected to the input end of the blood storage tank 4. Wherein the first plasma separating line 11 comprises a first plasma separator 111, the first plasma separator 111 is provided with a first blood inlet 111-1, a first plasma outlet 111-2 and a first blood cell outlet 111-3, the first plasma outlet 111-2 is provided with a plasma separating branch 14 connected to the inlet of the blood storage tank 4, and a plasma separating pump 141 is provided on the plasma separating branch 14 so as to draw the plasma of the first plasma separator 111 into the blood storage tank 4 through the plasma separating pump 141. The first plasma separator 111 is provided with a pressure detection device to perform detection of the separation pressure state of the first plasma separator 111.
One end of the blood input pipeline 12 is connected to the first blood inlet 111-1, and the other end of the blood input pipeline is connected to a blood guiding deep venous catheter preset in a patient, the blood guiding deep venous catheter is a puncture cannula before treatment, a blood pumping pump 121 is arranged on the blood input pipeline 12, and blood is pumped from the patient through the blood pumping pump 121 and is input into the first plasma separator 111.
The blood input line 12 is connected in parallel to a drug input device 122, and the drug input device 122 may select a quantitative or timed device such as a syringe to inject drugs into the blood input line 12 in a possible embodiment. In this embodiment, the drug input by the drug input device 122 may be an anticoagulant drug for placing blood coagulation. More specifically, heparin is used as the anticoagulant in this embodiment, and in other possible embodiments, heparin, a natural anticoagulant such as hirudin, or at least one of potassium salts such as sodium citrate and potassium fluoride, and calcium ion chelating agents such as EDTA, may be used as the anticoagulant.
The blood input pipeline 12 is further connected in series with an arterial pot 123 located at the rear end of the blood pumping pump 121 in the blood conveying direction, the arterial pot 123 is used for capturing air entering a blood path, meanwhile, 1-3 connectors are arranged on the arterial pot 123, the connectors can be used for discharging air gathered in the arterial pot 123, and meanwhile, the connectors are further connected with an arterial pressure detector to be used for measuring arterial negative pressure and play a role in monitoring arterial blood flow.
The blood return pipeline 13 is connected with the first blood cell outlet 111-3, a venous pot 131 is arranged between the blood return pipeline 13 and the first blood cell outlet 111-3, one end of the blood return pipeline 13 is connected with a vein of a patient, and the other end of the blood return pipeline is connected with the venous pot 131. The venous pot 131 also serves to trap air entering the blood circuit and serves as an air detection site. The venous pot 131 is provided with 1-3 connectors which can be used to vent air from the venous pot 131, and a venous pressure monitor (not shown) which can be used to determine the resistance to venous return is also connected to the connectors. In addition, the venous pot 131 may also be connected to an air detector (not shown) which uses an ultrasonic detection method, and specifically, the venous pot 131 is located between two ultrasonic transmitting and receiving probes.
The liver perfusion circulation passage 2 comprises a biochemical purification pipeline, an input pipe of the biochemical purification pipeline is connected with an output end of the blood storage tank 4, and an output end of the biochemical purification pipeline is connected with an input end of the blood storage tank 4 to form a circulation passage. Specifically, the biochemical purification pipeline comprises a circulation branch connected with the input end and the output end of the blood storage tank 4 and a total liver perfusion assembly 21 arranged on the circulation branch. It should be noted that, in this embodiment, the circulation branch located at the position of the total liver perfusion assembly 21 near the output end of the blood storage tank 4 is defined as a pre-hepatic circulation branch 221, and the circulation branch located at the position of the total liver perfusion assembly 21 near the input end of the blood storage tank 4 is defined as a post-hepatic circulation branch 222.
The output end of the circulation branch close to the blood storage tank 4 is provided with a peristaltic pump 23, namely the peristaltic pump 23 is arranged on the hepatic circulation branch 221 so as to pump the plasma of the patient in the blood storage tank 4 and the extracorporeal liver oxygen carrier into the total liver perfusion component 21 for biological purification. A peristaltic pump 23 is adopted to provide power for conveying the plasma of the patient and the oxygen carrier of the liver in vitro, and the peristaltic pump 23 can adjust the flow rate of liquid conveying.
In addition, the oxygenator 24 is also disposed on the hepatic anterior circulation branch 221, and can sufficiently oxygenate the plasma of the patient and the extracorporeal liver oxygen carrier, and supply oxygen to the extracorporeal liver oxygen carrier, so as to ensure the purification of the plasma of the patient in the total liver perfusion assembly 21.
The whole liver perfusion assembly 21 includes a whole liver 211 and a perfusion chamber 212 accommodating the whole liver 211, and in the embodiment of the present application, the perfusion chamber is at least partially made of a transparent material for easy operation and observation of perfusion.
Further, a temperature control device (not shown) is disposed in the perfusion chamber 212 for adjusting the internal temperature of the perfusion chamber 212, so as to simulate the body temperature state of a human body for purification treatment, and provide a stable external environment for the whole liver 211.
In the present application, the whole liver 211 is derived from animal liver, and fresh pig whole liver 211 can be used. The pipeline of circulation branch road with whole liver 211 is connected, simultaneously whole liver 211 is connected with bile recovery unit 213 to retrieve the bile and be used for parameter index to detect.
The pre-hepatic circulation branch 221 and the post-hepatic circulation branch 222 are respectively provided with a pressure detection device for detecting the pressure of the pre-hepatic circulation branch 221 and the post-hepatic circulation branch 222 so as to adaptively adjust the perfusion pressure, flow and flow rate of the circulation branches through the peristaltic pump 23, thereby ensuring that the whole liver 211 is in the best internal and external environment and exerting a good substitution function.
The patient plasma purified by the whole liver perfusion component 21 and the extracorporeal liver oxygen carrier return to the blood storage tank 4, and then the purified patient plasma obtained by separation through the plasma separation and return circulation path 3 is returned to the patient.
Specifically, the plasma separation and return circulation path 3 includes a second plasma separator 31, and the second plasma separator 31 is provided with a second blood inlet 31-1, a second plasma outlet 31-2, and a second blood cell outlet 31-3. The second blood inlet 31-1 is connected with the output end of the blood storage tank 4, and an infusion pump 32 is arranged between the second blood inlet 31-1 and the output end of the blood storage tank 4 and can provide power for inputting purified patient plasma and extracorporeal liver oxygen carriers into the plasma separation and return circulation passage 3; the second blood cell outlet 31-3 is connected with the input end of the blood storage tank 4 through a conduit 311, and the extracorporeal liver oxygen carrier separated by the second plasma separator 31 is returned to the blood storage tank 4 through the conduit 311 for circulating plasma separation; the second plasma outlet 31-2 is connected to a plasma return line 33, the other end of the second plasma return management device, which is away from the second plasma outlet 31-2, is connected to a venous pot 131 on the blood return line 13, and the venous pot 131 can also mix the blood cells separated by the first plasma separator 111 with the purified plasma of the patient and then return the mixture to the patient. And a plasma return pump 331 is arranged on the plasma return pipeline 33 to provide power for conveying purified plasma of the patient.
The second plasma separator 31 is provided with a pressure detection device for detecting the separation pressure state of the plasma separator. Furthermore, besides introducing pressure detection devices into the branch pipelines, a blood flow detection device can be arranged to detect the state of the bioartificial liver system in real time and provide reference data for confirming the state of the patient during treatment.
In addition, the output end of the blood storage tank 4, the liver perfusion circulation path 2 and the plasma separation and return circulation path 3 are connected through a three-way valve 41, and the conversion of the liver perfusion circulation path 2 and the plasma separation and return circulation path 3 can be realized through the three-way valve 41.
The utility model provides a biological artificial liver system of whole liver type, the patient's plasma that separates through the plasma separation circulation route 1 that is connected with the patient carries extremely in the blood storage tank 4, and with the external liver oxygen carrier in the blood storage tank 4 mixes, the external liver circulation route of back income carries out biological purification, and external liver circulation divide into liver perfusion circulation route 2 and plasma separation feedback circulation route 3, can adjust the perfusion pressure of external liver better, flow and velocity of flow, ensure that external liver is in the best inside and outside environment, make it can exert good substitute function, and plasma separation circulation route 1 and external liver circulation route synchronous cycle, the perfusion efficiency is improved, cycle time can be greatly shortened, the liver self-regeneration's opportunity is provided for the patient.
The operation of the whole liver bioartificial liver system of the present application will be described in detail below:
under the power provided by the blood pumping pump 121, the patient's blood passes through the first plasma separator 111, and toxic plasma and blood cells in the patient's blood are separated by the first plasma separator 111 in a mode plasma separation method, wherein the separated plasma flows out from the first plasma outlet 111-2 and enters the plasma separation branch 14, and the blood cells enter the venous pot 131 through the first blood cell outlet 111-3. The plasma of the patient is pumped into the blood storage tank 4 through the plasma separating pump 141 of the plasma separating branch 14, and enters the extracorporeal liver circulation path after being mixed with the extracorporeal liver oxygen carrier pre-stored in the blood storage tank 4. In the whole liver perfusion component 21, the whole liver 211 has the functions of detoxification, transformation, synthesis and the like on toxic plasma, and the in-vitro liver oxygen carrier can provide oxygen for the whole liver 211, so that the whole liver 211 can fully exert the functions of detoxification and metabolism on the plasma of a patient. The purified blood plasma and the oxygen carrier of the extracorporeal liver are returned to the blood storage tank 4 and then enter an extracorporeal separation and return circulation through the infusion pump 32, the second plasma separator 31 is used for separating the plasma after biological purification and the extracorporeal liver oxygen carrier, the extracorporeal liver oxygen carrier after separation is returned to the blood storage tank 4 from the second blood cell outlet 31-3 through the conduit 311, the purified plasma enters the plasma return pipeline 33 from the second plasma outlet 31-2, the purified plasma and the blood cells from the first blood cell outlet 111-3 are mixed into whole blood and then are returned to the body of the patient, the blood is subjected to the above process to complete the extracorporeal biological purification process, and various metabolic toxins and pathogenic factors in the body of the patient can be effectively eliminated, so that the treatment purpose is achieved.
In addition, the four Tibet miniature pigs are selected to be divided into an experimental group and a control group, the surgical partial ischemic liver failure modeling method is adopted to carry out surgical modeling on the Tibet miniature pigs, the biochemical conditions of the four Tibet miniature pigs are monitored respectively after surgery, and the liver failure model pigs of the experimental group and the control group are treated respectively on the fifth day after surgery. Specifically, two liver failure model pigs in an experimental group are treated by adopting the total liver type bioartificial liver system, two liver failure model pigs in a control group are treated by adopting a conventional internal treatment method, and the life cycle and biochemical conditions of the two groups of liver failure model pigs are compared.
After the total-liver bioartificial liver system is adopted to treat two liver failure model pigs of an experimental group for 8 hours, the system operates stably in the treatment process, the peristaltic pump can control the hepatic blood flow to be 1 ml/g hepatic tissue/minute, and meanwhile, the portal vein hepatic blood flow pressure in the treatment process is kept stable and basically maintained between 8 and 11 mmHg.
Specifically, referring to fig. 2a to 2d, by comparing the experimental group with the control group (the treatment group in the figure is the experimental group), the blood ammonia, blood lactic acid, total bilirubin and direct bilirubin of the liver failure model pig treated by the total liver type bioartificial liver system of the present application are all significantly improved, the survival time of the liver failure model pig of the experimental group exceeds 10 days, while two liver failure model pigs of the control group can only survive for 6 days and 8 days, that is, the total liver type bioartificial liver system of the present application has a good treatment effect on liver failure.
The foregoing is only a partial embodiment of the present application, and it should be noted that, for those skilled in the art, several modifications and decorations can be made without departing from the principle of the present application, and these modifications and decorations should also be regarded as the protection scope of the present application.

Claims (8)

1. A total-liver type bioartificial liver system is characterized in that: the device comprises a plasma separation circulation passage, a liver perfusion circulation passage and a plasma separation feedback circulation passage which are relatively independent, and further comprises a blood storage tank, wherein the blood storage tank is used for mixing plasma input through the plasma separation circulation passage and an external liver oxygen carrier, and the output end of the blood storage tank, the liver perfusion circulation passage and the plasma separation feedback circulation passage are connected through a three-way valve;
the plasma separation circulation passage comprises a blood input pipeline, a first plasma separation pipeline and a blood return pipeline, and the first plasma separation pipeline is connected with the input end of the blood storage tank;
the liver perfusion circulation passage comprises a biochemical purification pipeline, the biochemical purification pipeline is provided with a total liver perfusion component, the input end of the biochemical purification pipeline is connected with the output end of the blood storage tank, and the output end of the biochemical purification pipeline is connected with the input end of the blood storage tank;
plasma separation feedback circulation route includes that the second divides plasma circulation pipeline and returns the plasma pipeline, the second divide plasma circulation pipeline's input with the output of blood storage tank is connected, it connect in to return the plasma pipeline the second divide plasma circulation pipeline with between the blood feedback pipeline, the second divides plasma circulation pipeline including the second plasma separator that is equipped with second blood entry, second plasma export and second blood cell export, second blood entry with the output of blood storage tank is connected and is equipped with the transfer pump between the two, second blood cell export pass through the pipe with the input of blood storage tank is connected.
2. The bioartificial liver system of claim 1, wherein: first branch plasm way is including being equipped with the first blood separator of first blood entry, first plasma export, first blood cell export, and follow first plasma export is connected to the branch plasm branch road of blood storage tank, be equipped with the branch milk pump on the branch milk branch road.
3. The bioartificial liver system of claim 2, wherein: the blood input pipeline is connected with the first blood inlet, and a blood pumping pump is arranged on the blood input pipeline;
the blood return line is connected with the first blood cell outlet.
4. The bioartificial liver system of claim 1, wherein: the biochemical purification pipeline comprises a circulation branch connected with the input end and the output end of the blood storage tank, the total liver perfusion component is arranged on the circulation branch, and a peristaltic pump and an oxygenator are arranged on the circulation branch close to the output end of the blood storage tank.
5. The bioartificial liver system of claim 4, wherein: the whole liver perfusion assembly comprises a whole liver and a perfusion cabin body for accommodating the whole liver.
6. The bioartificial liver system of claim 5, wherein: the whole liver is derived from animal liver.
7. The bioartificial liver system of claim 5, wherein: the whole liver is connected with a bile recovery device for recovering bile.
8. The bioartificial liver system of claim 1, wherein: the plasma return pipeline is connected with the second plasma outlet, a plasma return pump is arranged on the plasma return pipeline, a vein kettle is arranged on the blood return pipeline, and the plasma return pipeline is connected to the vein kettle.
CN202011416329.8A 2020-12-04 2020-12-04 Total-liver type bioartificial liver system Active CN112604051B (en)

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Inventor after: Fu Yu

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Inventor after: Xue Weisong

Inventor after: Li Yang

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