CN115120799A

CN115120799A - Liver rescue system

Info

Publication number: CN115120799A
Application number: CN202210644464.0A
Authority: CN
Inventors: 赵强; 黄金波; 唐云华; 康骏; 李冶夫; 郭志勇; 何晓顺
Original assignee: First Affiliated Hospital of Sun Yat Sen University
Current assignee: First Affiliated Hospital of Sun Yat Sen University
Priority date: 2022-06-08
Filing date: 2022-06-08
Publication date: 2022-09-30
Anticipated expiration: 2042-06-08
Also published as: CN115120799B

Abstract

The invention provides a liver rescue system, comprising: an immune-privileged device for separating immune cells from other blood components from blood; a first container for storing a liver ex vivo; the first pipeline is respectively connected with the immune exemption device and the blood vessel of the human body; the second pipeline is respectively connected with the immune-immune exempting device and the in vitro liver; a third pipeline which is respectively connected with the isolated liver and the blood vessel of the human body; and the fourth pipeline is respectively connected with the immune-immune exempting device and the blood vessel of the human body. The liver rescue system can undertake corresponding multiple functions such as detoxify, synthesis, secretion through the liver of separation in vitro substitution patient's exhaustion liver, it separates into immunocyte and other blood components through the blood of immune exemption device with patient's output, do not contain immunocyte or only contain other blood components of minute quantity immunocyte and flow into the liver of separation in vitro, prevent that the liver of separation in vitro from taking place the immunological rejection reaction, the immunocyte can flow back to the patient in vivo through the fourth pipeline again, avoid influencing patient's immunocompetence.

Description

Liver rescue system

Technical Field

The invention relates to the technical field of medical equipment, in particular to a liver rescue system.

Background

When various pathogenic factors (such as viruses, alcohol, drugs and the like) act on the liver to cause serious damage, a large amount of liver cells are necrosed, the liver function is seriously hindered or decompensated, and a group of clinical symptoms mainly manifested by hepatic encephalopathy, blood coagulation mechanism disorder, jaundice, ascites and the like, namely liver failure, appear. At present, the clinical treatment of liver failure is mainly comprehensive treatment, and comprises three aspects of internal medicine basic treatment, artificial liver treatment and liver transplantation treatment. Medical drug therapy is mainly used for strengthening the function of the failing liver, but for the diseased liver, the function of the diseased liver is in a failure state, and the liver function lifting space is not large. Therefore, clinical artificial liver support therapy of 'replacing failure liver function' gradually appears, however, the artificial liver system can not reach the level of normal liver of human body in the aspects of cell number, space structure, physiological function and the like, and the treatment requirement of liver failure is difficult to meet.

Disclosure of Invention

The present invention is directed to solving at least one of the problems of the prior art. Therefore, the invention provides a liver rescue system which can replace the exhausted liver of a patient and can avoid immunological rejection reaction between immune cells in the body of the patient and the isolated liver.

According to the liver rescue system of the embodiment of the invention, the liver rescue system comprises:

an immune-privileged device for separating immune cells from other blood components from blood;

a first container for storing a liver ex vivo;

one end of the first pipeline is connected with the immune-exempting device, and the other end of the first pipeline can be connected with a blood vessel of a human body and is used for enabling blood in the human body to flow into the immune-exempting device;

one end of the second pipeline is connected with the immune exemption device, and the other end of the second pipeline can be connected with the isolated liver in the first container and is used for enabling other blood components to flow into the isolated liver;

one end of the third pipeline can be connected with the isolated liver in the first container, and the other end of the third pipeline can be connected with a human body blood vessel and is used for enabling other blood components passing through the isolated liver to flow back to the human body;

and one end of the fourth pipeline is connected with the immune exemption device, and the other end of the fourth pipeline can be connected with a blood vessel of a human body and is used for enabling immune cells to flow back to the human body.

The liver rescue system provided by the embodiment of the invention at least has the following beneficial effects:

the liver rescue system can replace the exhausted liver of a patient through the in vitro liver to bear various functions of corresponding detoxification, synthesis, secretion and the like, compared with artificial livers such as biological artificial livers, non-biological artificial livers and combined artificial livers, the in vitro liver is obtained from normal human livers, the cell function activity is high, the original three-dimensional frame and the surrounding matrix environment of the livers are maintained, and compared with xenogenic whole liver perfusion, the risk events such as immunological rejection, zoonosis propagation and the like caused by using xenogenic materials can be reduced. In addition, it should be noted that this embodiment has still set up immune exemption device, and immune exemption device can be with the blood separation of patient's output for immune cell and other blood components, does not contain immune cell or only contain other blood components of a minute quantity of immune cell and flow into the liver of separation in vitro, prevents that the liver of separation in vitro from taking place the immunological rejection reaction, and immune cell can avoid influencing patient's immunocompetence through fourth pipeline backward flow to the patient again.

In other embodiments of the present invention, the liver rescue system further comprises:

a second container connected to the second pipeline;

a repair liquid supply device connected to the second container for supplying a repair liquid to the second container so that other blood components are mixed with the repair liquid in the second container;

and one end of the fifth pipeline is connected to the second container, and the other end of the fifth pipeline can be connected with the human liver, so that part of other blood components mixed with the repair liquid can flow back to the human liver.

In other embodiments of the present invention, the liver rescue system further includes a three-way valve and a sixth pipeline, one end of the sixth pipeline is connected to the repairing liquid supply device, and the other end of the sixth pipeline is connected to the third pipeline through the three-way valve;

when the three-way valve is in a first state and the first pipeline, the third pipeline, the fourth pipeline and the fifth pipeline are connected with the human body, other blood components passing through the isolated liver can flow back to the human body from the third pipeline; when the three-way valve is in the second state and the first pipeline, the third pipeline, the fourth pipeline and the fifth pipeline are separated from the human body, the repair liquid passing through the isolated liver can flow back to the repair liquid supply device from the sixth pipeline.

In other embodiments of the invention, the liver rescue system is configured to: the flow of the liquid flowing into the isolated liver through the second pipeline is larger than the flow of the liquid flowing into the human body through the fifth pipeline.

In other embodiments of the invention, the liver rescue system further comprises at least one of the following devices:

the filter plug device is connected to the third pipeline;

the suspension device is connected in the first container and is used for suspending the isolated liver;

the atomizing device is connected with the first container and is used for adjusting the humidity in the first container;

and the secretion collecting device is connected to the first container and is used for collecting the secretion of the isolated liver.

In other embodiments of the invention, the immune-privileged device comprises:

a third container having a first inner cavity for containing a base liquid, a first inlet for allowing the base liquid to flow into the first inner cavity, and a first outlet in communication with the second pipeline;

a base liquid supply device connected to the third tank for supplying the base liquid to the third tank;

the filter tube is provided with a tube cavity, a second inlet and a second outlet, the tube cavity is used for containing blood, the second inlet is communicated with the first pipeline, the second outlet is communicated with the fourth pipeline, the filter tube is located in the first inner cavity and used for filtering the blood, so that immune cells are retained in the tube cavity, and other blood components are mixed with the base liquid in the first inner cavity through the tube wall.

In other embodiments of the invention, the filter tube is disposed in a serpentine configuration within the first lumen.

In other embodiments of the present invention, the cross-sectional area of the lumen is tapered in the direction of flow of the blood.

In other embodiments of the invention, the immune-privileged device further comprises:

a fourth container having a second lumen, a third inlet in communication with the first outlet for flow of other blood components into the second lumen, and a third outlet in communication with the second conduit for flow of other blood components out of the second lumen;

and the first suction piece is positioned in the second inner cavity and is used for sucking immune cells in other blood components.

In other embodiments of the present invention, the immune-privileged device further comprises a second sorbent material located within the second lumen for adsorbing inflammatory factors from other blood components.

Additional aspects and advantages of the invention 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 invention.

Drawings

The invention is further described with reference to the following figures and examples, in which:

fig. 1 is a schematic view of a liver rescue system in a first embodiment of the invention;

fig. 2 is a schematic diagram of a liver rescue system in a second embodiment of the invention;

fig. 3 is a schematic view of a liver rescue system in a third embodiment of the present invention;

FIG. 4 is a schematic view of the liver rescue system of FIG. 3 in a maintenance mode;

FIG. 5 is a schematic view of an immune-privileged device in accordance with an embodiment of the present invention;

FIG. 6 is a schematic view showing the structure of the wall of the filtering tube in FIG. 5;

FIG. 7 is a cross-sectional view of the first suction attachment of FIG. 5;

fig. 8 is a sectional view of the second adsorption member of fig. 5.

Reference numerals:

the immune-immune device 100, the third container 110, the first inner cavity 111, the first inlet 112, the first outlet 113, the filter tube 120, the lumen 121, the second inlet 122, the second outlet 123, the filter membrane 124, the filter holes 125, the base liquid supply device 130, the fourth container 140, the second inner cavity 141, the third inlet 142, the third outlet 143, the first adsorbent 150, the first adsorbent bead 151, the specific antibody layer 152, the second adsorbent 160, the second adsorbent bead 161, the inflammatory factor adsorbent layer 162

A first container 210, a second container 220;

a first pipeline 310, a second pipeline 320, a first branch 321, a second branch 322, a first pipe 323, a second pipe 324, a third pipeline 330, a third pipe 331, a fourth pipe 332, a fourth pipeline 340, a fifth pipeline 350, a sixth pipeline 360, a seventh pipeline 370;

a repair liquid supply device 400;

three-way valve 500, first opening 510, second opening 520, third opening 530;

a membrane lung 610, a filter plug device 620, a hanging device 630, a centrifugal device 640 and a water bath device 650;

isolated liver A, femoral artery B, femoral vein C, in vivo liver D.

Detailed Description

Reference will now be made in detail to embodiments of the present invention, 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 accompanying drawings are illustrative only for the purpose of explaining the present invention, and are not to be construed as limiting the present invention.

In the description of the present invention, it should be understood that the orientation or positional relationship referred to in the description of the orientation, such as the upper, lower, front, rear, left, right, etc., is based on the orientation or positional relationship shown in the drawings, and is only for convenience of description and simplification of description, and does not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus, should not be construed as limiting the present invention.

In the description of the present invention, the meaning of a plurality is one or more, the meaning of a plurality is two or more, and the above, below, exceeding, etc. are understood as excluding the present numbers, and the above, below, within, etc. are understood as including the present numbers. If the first and second are described for the purpose of distinguishing technical features, they are not to be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated or implicitly indicating the precedence of the technical features indicated.

In the description of the present invention, unless otherwise explicitly limited, terms such as arrangement, installation, connection and the like should be understood in a broad sense, and those skilled in the art can reasonably determine the specific meanings of the above terms in the present invention in combination with the specific contents of the technical solutions.

In the description of the present invention, reference to the description of "one embodiment", "some embodiments", "illustrative embodiments", "examples", "specific examples", or "some examples", etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.

The invention provides a liver rescue system, which can temporarily replace a failing liver in a patient body by using an allogeneic liver perfused in vitro, and can separate blood input into the liver in vitro by an immune exemption device so as to avoid immune rejection caused by immune cells in the blood entering the liver in vitro, and the liver rescue system is specifically described below by combining with an attached drawing.

Referring to fig. 1, there is shown a schematic view of a liver rescue system in a first embodiment of the present invention, in which arrows indicate the flow direction of liquid. The liver rescue system comprises the immune-privileged device 100, the first container 210, the second pipeline 320, the third pipeline 330 and the fourth pipeline 340, wherein the immune-privileged device 100 can separate blood output by a patient into immune cells (mainly comprising leucocytes and the like) and other blood components (mainly comprising red blood cells, platelets, plasma and the like), namely other components in the blood different from the immune cells. First container 210 is used for depositing separation liver A (separation liver A is the allogeneic liver that donates), is provided with the interface that is used for with each pipeline intercommunication on the container wall of first container 210, or the through-hole that supplies each pipeline to pass.

First pipeline 310 one end is connected to immune-privileged device 100, and the other end can be connected with the human body to make the internal blood of patient flow into immune-privileged device 100 and carry out the component separation, specifically, first pipeline 310 is connected with human blood vessel, for example can communicate with patient's femoral artery B.

Second pipeline 320 one end is connected in immune exemption device 100, the other end can be connected with the separation liver A in the first container 210, make other blood components that are separated by immune exemption device 100 can flow in separation liver A through second pipeline 320, on the one hand, perfuse separation liver A, guarantee separation liver A's biological activity, on the other hand separation liver A exerts multiple functions such as detoxification, synthesis, secretion of normal liver, blood ammonia in patient's blood, bilirubin and other metabolic waste are purified, release liver synthetic fully to get into blood simultaneously, thereby the effect of substituting patient's liver is exerted. Specifically, one end of the second pipeline 320 connected to the isolated liver a is divided into a first branch pipe 321 and a second branch pipe 322, and the two branch pipes are respectively communicated with the portal vein and the hepatic artery of the isolated liver a.

One end of the third pipeline 330 can be connected to the isolated liver a in the first container 210, and the other end can be connected to the human body, so as to enable other blood components passing through the isolated liver a to flow back to the human body, specifically, one end of the third pipeline 330 is communicated with the vena cava of the isolated liver a, and the other end is connected to a blood vessel of the human body, for example, communicated with the femoral vein C of the human body, and by combining the first pipeline 310 and the second pipeline 320, the blood of the patient can circulate in vivo and in vitro.

One end of the fourth pipeline 340 is connected to the immune-exempting device 100, and the other end can be connected with the human body, so that the immune cells separated by the immune-exempting device 100 flow back to the human body, the immune ability of the patient is not influenced, the immune cells do not flow into the isolated liver A to cause immune rejection, and the survival of the isolated liver A is guaranteed.

As can be seen from the above, the liver rescue system in this embodiment can replace the failing liver of the patient with the isolated liver a to undertake various functions such as detoxification, synthesis, secretion, and the like, and compared with artificial livers such as biological artificial livers, non-biological artificial livers, and combined artificial livers, the isolated liver a is derived from a normal human liver, has high cellular functional activity, and simultaneously maintains the original three-dimensional frame and surrounding matrix environment of the liver, and compared with xenogenic whole liver perfusion, can reduce the incidence of risk events such as immune rejection, zoonosis spread, and the like caused by using xenogenic materials. Furthermore, it should be noted that, the present embodiment further provides the immune-privileged device 100, the immune-privileged device 100 can separate the blood output by the patient into immune cells and other blood components, and the other blood components that do not contain immune cells or only contain a very small amount of immune cells flow into the isolated liver a, so as to prevent the isolated liver a from generating immune rejection, and the immune cells can flow back into the patient through the fourth pipeline 340, so as to avoid affecting the immunocompetence of the patient.

The pipeline according to the present invention may be a single continuous pipe or a plurality of pipes communicating with each other.

It should be noted that the separation liver a of this embodiment can adopt partial liver, compare with the whole liver perfusion, partial liver perfusion parameter is easily regulated and control, partial liver perfuses comparatively fully, can reduce the perfusion requirement, promotes separation liver a's working life, reduces treatment risk and reduces treatment cost. In addition, the shortage of liver supply is a main contradiction in the field of transplantation, and compared with the whole liver, the partial liver perfusion can realize the repeated utilization of one liver, thereby improving the utilization rate of scarce resources

In addition, in some other embodiments, the liver rescue system may further include other devices, for example, referring to fig. 1, the liver rescue system further includes a membrane lung 610, the membrane lung 610 is connected to the second pipeline 320 for oxygenating other blood components flowing therethrough, and the other blood components flow into the ex-vivo liver a after being oxygenated. It will be appreciated that in this case the second conduit 320 comprises at least two lengths of tubing, one connected between the membrane lung 610 and the immune-privileged device 100 and the other connected between the membrane lung 610 and the isolated liver a.

The liver rescue system may further comprise a plurality of pumps, not shown, for effecting a directed flow of the liquid, e.g. driving the flow of the other blood components towards the extracorporeal liver a and driving the flow of the other blood components flowing from the extracorporeal liver a towards the human body.

The liver rescue system may further include a thrombus filter 620, and the thrombus filter 620 is connected to the third line 330 for separating thrombus and other impurities that may be generated during the perfusion process.

When the isolated liver a is a partial liver, the liver rescue system may further include a suspension device 630, the suspension device 630 is disposed in the first container 210, and the sickle ligament and the coronary ligament on the surface of the partial liver are fixed by the suspension device 630, so as to ensure that the partial liver is not ischemic due to squeezing during perfusion.

When separation liver A adopted partial liver, because partial liver cuts the section and lacks liver capsule cover, liquid evaporation capacity is great, consequently liver rescue system can also include humidity transducer and atomizing device not shown, atomizing device connects in first container 210, humidity transducer carries out real-time measurement to humidity to return controlling means with data, controlling means adjusts atomizing device according to measured humidity, ensures to fill humidity around the liver segment and maintains in internal normal humidity within range.

The liver rescue system may further comprise a secretion collecting device, not shown, connected to the first container 210, capable of collecting secretions (e.g. bile) of the isolated liver a through the biliary tract cannula.

Referring to fig. 2, a schematic diagram of a liver rescue system in a second embodiment of the present invention is shown, which includes various liver rescue systems in the first embodiment, and on this basis, the liver rescue system in this embodiment further includes a second container 220, a repair liquid supply device 400 and a fifth pipeline 350, the repair liquid supply device 400 is used for supplying repair liquid to the second container 220, so that other blood components are mixed with the repair liquid to repair the three-dimensional liver a and the exhausted liver of the patient, which will be described in detail below with reference to the drawings.

The second container 220 is connected to the second pipeline 320, specifically, the second pipeline 320 includes a first pipeline 323 and a second pipeline 324, one end of the first pipeline 323 is communicated with the other blood component outlet of the immune-privileged device 100, the other end is communicated with an inlet of the second container 220, one end of the second pipeline 324 is communicated with an outlet of the second container 220, and the other end is respectively communicated with the first branch pipe 321 and the second branch pipe 322, so that the other blood components flowing out of the immune-privileged device 100 firstly flow into the second container 220, and then flow into the isolated liver a after being mixed with the repairing liquid in the second container 220.

The repairing liquid supplying device 400 is communicated with the second container 220, specifically, communicated with a seventh pipeline 370, one end of the seventh pipeline 370 is communicated with a liquid outlet of the repairing liquid supplying device 400, and the other end is communicated with another liquid inlet of the second container 220. The repair liquid supply device 400 may be a container for containing repair liquid, and a pump may be further disposed on the seventh pipeline 370 to drive the repair liquid to flow into the second container 220.

One end of the fifth pipeline 350 is connected to the second container 220, and the other end can be connected to the human liver, specifically, the fifth pipeline 350 can be communicated with the portal vein of the internal liver D, so that part of the other blood components mixed with the repair liquid flows back to the human liver, that is, the liver rescue system of the embodiment has both substitution and repair functions, one part of the other blood components mixed with the repair liquid continues to flow to the isolated liver a through the second pipeline 320, and the other part of the other blood components flows back to the human body through the fifth pipeline 350, so that on one hand, the liver rescue system can repair the isolated liver a to a certain extent, enhance the metabolic function and metabolic efficiency of the isolated liver a, and prolong the working time of the isolated liver a, and on the other hand, the liver disease in the patient can be repaired while the isolated liver a plays a role of temporarily substituting the liver, so as to recover the disease, the dependence of the patient on the system is reduced, so that the liver of the patient can still maintain normal physiological functions after the patient is separated from the liver rescue system, and more waiting time is strived for subsequent treatment such as liver transplantation operation.

It should be noted that the fifth pipeline 350 may be completely independent from the second pipeline 320, or may have a common pipeline with the second pipeline 320, specifically, as shown in the figure, the fifth pipeline 350 shares a part of the second pipeline 324 with the second pipeline 320, and the membrane lung 610 may be connected to the common second pipeline 324.

In other embodiments, the liver rescue system may further include a centrifugal device 640, the centrifugal device 640 is connected to the third pipeline 330, the mixed solution flowing out of the isolated liver a and mixed with the repairing solution and other blood components (which may include other components, such as a base solution described below, etc.) passes through the centrifugal device 640 and is separated again, the separated other blood components flow back to the human body, and the waste solution is discarded, so that the outflow flow rate and the inflow flow rate of the patient can be approximately balanced.

Based on the above, the liver rescue system may further include a water bath device 650, the water bath device 650 is connected to the third pipeline 330, specifically, downstream of the centrifugal device 640, and the other blood components separated by the centrifugal device 640 are slowly heated to the physiological temperature range in the water bath device 650 and then flow into the human body.

In other embodiments, the flow rate of the liquid flowing into the isolated liver a through the second pipeline 320 is greater than the flow rate of the liquid flowing into the human body through the fifth pipeline 350, so that on one hand, a large amount of other blood components which are not processed by the isolated liver a can be prevented from directly flowing into the human body, and on the other hand, the imbalance of the liquid in and out of the human body caused by the excessive repair liquid flowing into the human body can be avoided. Specifically, the flow ratio of the two may be greater than 5: 1. the difference in flow rates between the two can be adjusted by means of a control valve or the like.

Referring to fig. 3, a schematic diagram of a liver rescue system in a third embodiment of the present invention includes various liver rescue systems in the second embodiment, and further includes a three-way valve 500 and a sixth pipeline 360, one end of the sixth pipeline 360 is connected to the repair liquid supply device 400, and the other end is connected to the third pipeline 330 through the three-way valve 500, specifically, the three-way valve 500 has three openings, namely a first opening 510, a second opening 520 and a third opening 530, for example, the first opening 510 is located at the right side of the three-way valve 500, the second opening 520 is located at the left side of the three-way valve 500, the third opening 530 is located at the lower side of the three-way valve 500, the third pipeline 330 includes a third pipeline 331 and a fourth pipeline 332, one end of the third pipeline 331 can be connected to the liver a ex vivo, the other end is communicated with the first opening 510 of the three-way valve 500, one end of the fourth pipeline 332 is communicated with the second opening 520 of the three-way valve 500, the other end can be connected to a human body, and one end of the sixth pipe 360 is connected to the repair liquid supply device 400 and the other end is communicated with the third opening 530 of the three-way valve 500. The three-way valve 500 can be controlled to adjust the operating state in such a way that when it is in the first state, the first opening 510 is in communication with the second opening 520 and the first opening 510 is disconnected from the third opening 530, and when it is in the second state, the first opening 510 is disconnected from the second opening 520 and the first opening 510 is closed to the third opening 530.

Based on the structure, the liver rescue system of the embodiment can be switched between the first working mode and the second working mode, when the liver rescue system is in the first working mode, the replacement and repair functions can be realized, and when the liver rescue system is in the second working mode, the maintenance function of the in-vitro liver A can be realized. Specifically, when the liver rescue system is connected to the human body, that is, the first pipeline 310, the third pipeline 330, the fourth pipeline 340 and the fifth pipeline 350 are all connected to the corresponding positions of the human body, the three-way valve 500 is in the first state, the sixth pipeline 360 is substantially in the disconnected state, the blood of the human body flows into the immune-immune exempting device 100 through the first pipeline 310, the blood is separated into immune cells and other blood components, the immune cells flow back into the human body through the fourth pipeline 340, the other blood components flow into the second container 220 through the second pipeline 320 (specifically, the first pipeline 323), meanwhile, the repairing liquid in the repairing liquid supply device 400 flows into the second container 220 through the seventh pipeline 370, so that the other blood components and the repairing liquid are mixed to obtain a mixed liquid, a part of the mixed liquid continuously flows into the isolated liver a through the second pipeline 320 (specifically, the second pipeline 324), and flows out after being processed by the isolated liver a, and flows into the human body through the third line 330 and another part flows into the human liver through the fifth line 350.

When the liver rescue system is disconnected from the human body, that is, the first pipeline 310, the third pipeline 330, the fourth pipeline 340 and the fifth pipeline 350 are all disconnected from the human body, no external blood is input into the system, at this time, the liver rescue system is substantially as shown in fig. 4, the three-way valve 500 is in the second state, the sixth pipeline 360 is communicated, the third pipeline 330 is disconnected from the three-way valve 500, the repairing liquid in the repairing liquid supply device 400 flows into the second container 220 through the seventh pipeline 370, and then flows into the isolated liver a through a part of the second pipeline 320 (specifically, the second pipeline 324), so as to maintain the biological activity of the isolated liver a, the repairing liquid flowing out of the isolated liver a flows back to the repairing liquid supply device 400 through a part of the third pipeline 330 (specifically, the third pipeline 331) and the sixth pipeline 360, so as to realize the circulating perfusion of the isolated liver a, the liver a rescue system of the embodiment can be switched between the treatment mode and the maintenance mode, the maintenance of separation liver A and the treatment of patient have been realized through same equipment, need not to increase solitary separation organ preservation equipment, can reduce cost, and in addition, separation liver A need not to shift between a plurality of equipment, has reduced separation liver A's damage, helps prolonging separation liver A's life-span.

It should be noted that the liver rescue system may further include a red blood cell supply device, not shown, which introduces the suspended red blood cells of the same type as the patient into the second container 220, and mixes the red blood cells with the repair liquid in the second container 220 to form a perfusion liquid containing the red blood cells as a main component.

It should be noted that, when the fifth pipeline 350 is separated from the human body, it is usually closed by a device, but of course, a control valve may also be provided to control the on/off of the fifth pipeline 350, for example, when the liver rescue system operates in the treatment mode, the control valve controls the fifth pipeline 350 to be in the open state, and when the liver rescue system operates in the maintenance mode, the control valve controls the fifth pipeline 350 to be in the open state.

Referring to fig. 1 and 5, which are schematic views illustrating an immune-privileged device 100 according to an embodiment of the invention, solid arrows in fig. 5 indicate an inflow direction of a base fluid and an outflow direction of a mixed fluid, and dotted arrows indicate an inflow direction and an outflow direction of blood. The immune-immune exempting device 100 comprises a third container 110, a filter tube 120 and a base liquid supply device 130, wherein the third container 110 has a first inner cavity 111 for containing a base liquid, and the base liquid can be isotonic liquid containing erythrocyte nutrition protection factors, which can create a physiological environment for keeping erythrocytes in normal activity, reduce erythrocyte injury in vitro and can be used as a carrier of other blood components, and the components of the base liquid can adopt the prior art, and are not limited herein. The third container 110 further has a first inlet 112 and a first outlet 113, both of which are communicated with the first inner cavity 111, the first inlet 112 is used for base fluid to flow into the first inner cavity 111, and the first outlet 113 is used for base fluid to flow out of the first inner cavity 111, so that other blood components mixed with the base fluid can continuously flow out of the first inner cavity 111, and the base fluid is continuously supplied into the first inner cavity 111.

The filter tube 120 is a main device for separating immune cells from other blood components, and the separation of blood components is realized by means of physical filtration. The filter tube 120 has a lumen 121, and the lumen 121 is used to contain blood so that the blood can be confined in the lumen to direct the flow. Filter tube 120 also has a second inlet 122 and a second outlet 123, both in communication with lumen 121, second inlet 122 for blood to flow into lumen 121 and second outlet 123 for blood to flow out of lumen 121. Referring to fig. 6, the wall of the filtering pipe 120 is provided with a plurality of filtering holes 125, and the diameter of the filtering holes 125 needs to satisfy certain restrictions: the filter can block immune cells with larger diameter and can allow other blood components such as red blood cells, platelets, plasma and the like to pass through, and since the immune cells are mainly white blood cells, the diameter of the white blood cells is usually larger than 9 microns, in some embodiments, the diameter of the filter hole 125 is less than or equal to 9 microns so as to meet the filtering requirement of most immune cells.

When the blood separation device is used, blood is introduced into the filter tube 120 through the second inlet 122, and in the process of flowing of the blood in the lumen 121, other blood components such as red blood cells, platelets and plasma pass through the pore walls through the micropores under the action of gravity, so that the other blood components enter the base liquid to form a mixed liquid, the mixed liquid mainly contains the other blood components such as the red blood cells, the platelets and the plasma and only contains a small amount of immune cells with the diameter smaller than 9 micrometers, and the blood at the tail end of the lumen 121 mainly contains the immune cells, so that the separation of the blood components is realized. The blood enriched in immune cells in lumen 121 may continue to flow back into the patient

In other embodiments of the immune-privileged device 100, referring to fig. 5, the filter tube 120 is tortuous within the first lumen 111 to increase the length of the filter tube 120, thereby increasing the flow distance of blood within the filter tube 120 to enhance the filtering effect. The filter tube 120 has various zigzag forms, such as an S-shaped bend in the figure, and it should be noted that there is a gap between the bent portions of the filter tube 120, so that other blood components filtered out can be mixed into the base liquid.

In other embodiments, the cross-sectional area of the lumen 121 is gradually reduced along the flowing direction of the blood in the lumen 121, and the pressure generated by the gradient difference of the inner tube diameter provides effective filtering pressure for blood filtering, so that the filtering effect can be further improved by combining the gravity effect.

Referring to fig. 6, in other embodiments, the wall of the filtering tube 120 includes multiple filtering membranes 124, each filtering membrane 124 has a filtering hole 125, and since the filtering membranes 124 are stacked and the filtering holes 125 of the filtering membranes 124 are misaligned, other blood components need to pass through the filtering holes 125 of the multiple filtering membranes 124 to penetrate through the wall of the filtering hole, so as to further improve the blocking effect on the immune cells.

Referring to fig. 5, in other embodiments, the cross-sectional area of the third container 110 is gradually reduced along the top-to-bottom direction, i.e., the third container 110 is substantially funnel-shaped, and the first outlet 113 is disposed at the bottom of the third container 110, so that other blood components (including red blood cells and platelets) can be collected at the bottom of the third container 110 for being discharged through the first outlet 113, and thus the cells are prevented from being retained in the third container 110.

As mentioned above, since the diameter of part of the immune cells is small, the part of the immune cells may enter the basic solution through the wall of the filtering tube 120, causing the rejection reaction of the liver a in vitro, and the diameter of the part of the immune cells is similar to the diameter of the cells in other blood components, so that the physical filtering method is not suitable. Based on this, in other embodiments, the immune-privileged device 100 further includes an adsorption structure, specifically including the fourth container 140 and the first adsorption part 150, and the first adsorption part 150 further removes the residual immune cells by chemisorption.

The fourth container 140 has a second inner chamber 141, a third inlet 142 and a third outlet 143, the second inner chamber 141 is used for containing the mixed solution, the third inlet 142 and the third outlet 143 are both communicated with the second inner chamber 141, and in addition, the third inlet 142 is also communicated with the first outlet 113 through a pipe, so that other blood components mixed with the base solution can flow into the second inner chamber 141 through the third inlet 142 and flow out of the second inner chamber 141 through the third outlet 143.

First suction attachment 150 is located second inner chamber 141, and first suction attachment 150 can the specific adsorption mix the immune cell in other blood components, and can not adsorb other blood components, through the combination of above-mentioned physical filtering mode with the chemisorption mode, can very big reduction mix the content of immune cell in the liquid, when mixed liquid gets into separation liver A, can avoid separation liver A to take place rejection.

Referring to fig. 7, a specific implementation manner of the first suction attachment 150 includes a first suction bead 151 and a specific antibody layer 152, the specific antibody layer 152 is attached to the surface of the first suction bead 151, the specific antibody layer 152 will specifically bind to surface antigens of immune cells that are not physically filtered out in the mixed solution, and the escaped immune cells are further removed. Specifically, specific antibody layer 152 includes specific antibody CD4 or specific antibody CD 8. The specific antibody CD4 can be specifically combined with cytotoxic T cells with small volume in immune cells, and the specific antibody CD8 can be specifically combined with helper T cells, so that residual small lymphocytes which cannot be filtered by the filter tube 120 can be effectively adsorbed.

In other embodiments, referring to fig. 5 and 8, the immune-privileged device further includes a second adsorbent member 160, and the second adsorbent member 160 is disposed in the second inner cavity 141 and is used for adsorbing inflammatory factors in the mixed solution. Specifically, the second adsorption member 160 includes a second adsorption bead 161 and an inflammatory factor adsorption layer 162, and the inflammatory factor adsorption layer 162 is attached to an outer surface of the second adsorption bead 161.

It should be noted that the fourth container 140 has a container cover (not shown) capable of being opened and closed, and when the first absorbing member 150 and/or the second absorbing member 160 are used for a certain period of time, the first absorbing member 150 and the second absorbing member 160 can be replaced to ensure the absorbing effect.

Referring to fig. 5, in other embodiments, the third outlet 143 of the fourth container 140 is higher than the third inlet 142, that is, the mixed liquid flows in a direction from bottom to top, so that the mixed liquid can flow through the adsorbing members, the contact time between the mixed liquid and the adsorbing members is increased, and the adsorbing capacity of the adsorbing members is fully exerted, for example, the third outlet 143 is located at the top of the fourth container 140, and the third inlet 142 is located at the bottom of the fourth container 140.

Based on the liver rescue system in the third embodiment, the specific use process is as follows:

1. the donation and supply liver is obtained, the donation and supply liver is dissected to form different liver segments or parts of liver with larger volume, each part of liver completely retains hepatic artery main branch, portal vein main branch and vena cava main branch, tiny bile duct on hepatic section is ligated, and main intrahepatic bile duct is intubated.

2. Estimating the blood supply quantity required by part of the liver, and adjusting and setting perfusion parameters. According to the size of partial liver blood vessels, selecting proper hepatic artery, portal vein and vena cava intubation types. For filling into the first container 210 after finishing liver trimming.

3. After the liver is loaded, the device is operated in a test mode and partial liver functions are evaluated, the three-way valve 500 is in the second state, the sixth pipeline 360 is communicated, the third pipeline 330 is disconnected from the three-way valve 500, the repairing liquid in the repairing liquid supply device 400 flows into the second container 220 through the seventh pipeline 370, meanwhile, the suspended red blood cells of the same type as the patient are input into the second container 220 by the red blood cell supply device and are mixed with the repairing liquid in the second container 220, and therefore the perfusate containing the red blood cells as main components is formed. After flowing out from the second container 220, the perfusion fluid flows through the membrane lung 610 for oxygenation, and after oxygenation is finished, the perfusion fluid flows into the isolated liver a through a part of the second pipeline 320 (specifically, the second pipeline 324), so as to maintain the biological activity of the isolated liver a, and the perfusion fluid flowing out of the isolated liver a flows back to the repair fluid supply device 400 through a part of the third pipeline 330 (specifically, the third pipeline 331) and the sixth pipeline 360 to form a closed loop circulation. Comprehensively evaluating the appearance of the liver, biochemical indexes of perfusion liquid, biochemical indexes of bile and perfusion parameters, and judging whether the functional state of the liver of a perfusion part meets the system operation standard.

4. If the perfusion partial liver function state meets the system operation standard, respectively implanting puncture tubes into femoral artery, femoral vein and portal vein of patients with liver failure, connecting the first pipeline 310 and the fourth pipeline 340 with two puncture tubes of femoral artery, connecting the third pipeline 330 with the puncture tube of femoral vein, connecting the fifth pipeline 350 with the puncture tube of portal vein, and the three-way valve 500 being in the first state, the sixth pipeline 360 being in the disconnected state substantially, the human blood flowing into the filter tube 120 through the first pipeline 310, being separated into immune cells and other blood components, the immune cells flowing back to the femoral artery B of human body through the fourth pipeline 340, the other blood components being mixed with the base liquid in the first inner cavity 111 of the third container 110, flowing into the fourth container 140 after mixing, adsorbing the residual immune cells and inflammatory factors through the first adsorption piece 150 and the second adsorption piece 160, after the adsorption is completed, the fluid flows into the second container 220 through the second pipeline 320 (specifically, the first pipeline 323), and meanwhile, the repairing fluid in the repairing fluid supply device 400 flows into the second container 220 through the seventh pipeline 370, so that other blood components are mixed with the repairing fluid, a part of the mixed fluid continuously flows into the isolated liver a through the second pipeline 320 (specifically, the second pipeline 324), flows out after being treated by the isolated liver a, and flows into the femoral vein C of the human body through the third pipeline 330, and the other part of the mixed fluid flows into the portal vein of the liver D in the human body through the fifth pipeline 350, so that the circulation is established.

Based on the above, some embodiments of the present application have the following effects:

1. the liver rescue system in the embodiment is based on a 'substitution and repair function' treatment logic, the diseased liver is temporarily replaced by the liver perfused in vitro, meanwhile, repair measures for the diseased liver are added, the diseased liver function can be recovered, the dependence of a patient on the system is reduced, the liver of the patient can still maintain normal physiological functions after the patient is separated from the liver rescue system, and more waiting time is strived for subsequent treatment such as liver transplantation operation. In addition, the liver rescue system simultaneously carries out certain repair on the liver perfused in vitro, enhances the metabolic function and the metabolic efficiency of the liver in vitro, prolongs the working time of the liver in vitro, and increases the stability of the system performance

2. The liver rescue system in the embodiment adopts the isolated human liver as the substitute liver, compared with the traditional artificial liver, the material of the liver rescue system is derived from the normal human liver, the cell function activity is high, and the original three-dimensional frame and the surrounding matrix environment of the liver are maintained. Compared with xenogenic whole liver perfusion, the method can reduce the incidence rate of risk events such as immunological rejection, zoonosis spread and the like caused by using xenogenic materials; meanwhile, the system can adopt partial liver, compared with the whole liver perfusion, the partial liver perfusion parameters are easy to regulate and control, the partial liver perfusion is sufficient, the perfusion requirement can be reduced, the working life of the partial liver is prolonged, the treatment risk is reduced, and the treatment cost is reduced.

3. The liver rescue system in the embodiment is provided with the immune exemption device, and immune cells including lymphocytes and leukocytes can be effectively filtered by adopting physical filtration or the combination of the physical filtration and chemical adsorption, so that the in vitro liver is prevented from having immune rejection. Compared with the mode of separating immune cells by a centrifuge which is commonly used at present, the damage to other components in blood including red blood cells can be reduced, and the filtering effect is better.

4. The liver rescue system in the embodiment is provided with the inflammation isolation device, the systemic inflammatory response syndrome usually occurs in the body of a liver failure patient, and if inflammatory factors enter the in-vitro perfusion system without limitation, an inflammation storm is bound to spread to the in-vitro perfusion liver, so that the system fails. The inflammation isolation device can remove inflammatory factors, ensure that the liver rescue system is in an inflammation isolation state, and improve the stability of the system.

The embodiments of the present invention have been described in detail with reference to the accompanying drawings, but the present invention is not limited to the above embodiments, and various changes can be made within the knowledge of those skilled in the art without departing from the gist of the present invention. Furthermore, the embodiments of the present invention and the features of the embodiments may be combined with each other without conflict.

Claims

1. A liver rescue system, comprising:

a first container for storing a liver ex vivo;

a first pipeline, one end of which is connected with the immune-privileged device and the other end of which can be connected with a blood vessel of a human body, and is used for leading blood in the human body to flow into the immune-privileged device;

2. The liver rescue system according to claim 1, further comprising:

a second container connected to the second pipeline;

3. The liver rescue system according to claim 2, further comprising a three-way valve and a sixth pipeline, one end of the sixth pipeline being connected to the repair liquid supply device, and the other end being connected to the third pipeline through the three-way valve;

4. The liver rescue system of claim 2, wherein the liver rescue system is configured to: the flow of the liquid flowing into the isolated liver through the second pipeline is larger than the flow of the liquid flowing into the human body through the fifth pipeline.

5. The liver rescue system of claim 2, further comprising at least one of the following devices:

the filter plug device is connected to the third pipeline;

the suspension device is connected in the first container and used for suspending the in vitro liver;

6. The liver rescue system of claim 1, wherein the immune-privileged device comprises:

a base liquid supply device connected to the third container for supplying the base liquid to the third container;

the filter tube is provided with a tube cavity, a second inlet and a second outlet, the tube cavity is used for containing blood, the second inlet is communicated with the first pipeline, the second outlet is communicated with the fourth pipeline, the filter tube is positioned in the first inner cavity and used for filtering the blood, so that immune cells are retained in the tube cavity, and other blood components are mixed with the base liquid in the first inner cavity through the tube wall.

7. The liver rescue system of claim 6, wherein the filter tube is tortuous within the first lumen.

8. The liver rescue system of claim 6, wherein the lumen has a decreasing cross-sectional area in the direction of flow of the blood.

9. The liver rescue system of claim 6, wherein the immune-privileged device further comprises:

10. The liver rescue system of claim 9, wherein the immune-privileged device further comprises a second sorbent in the second lumen for adsorbing inflammatory factors from other blood components.