Bioartificial liver support system

Abstract

The invention provides a bioartificial liver supporting system which at least comprises a blood input branch pipeline, a plasma separation branch pipeline, a biological purification branch pipeline and a plasma return branch pipeline which are connected in sequence, and a liquid separation bottle is arranged between the biological purification branch pipeline and the plasma return branch pipeline; the liquid separation bottle comprises a bottle body, at least three partition plates are arranged in the bottle body, the heights of the partition plates are sequentially reduced in the circumferential direction so that the interior of the bottle body can be at least divided into three chambers with the water level heights sequentially reduced in the circumferential direction, the biological purification branch pipeline is communicated with the chamber with the highest water level height, and the slurry return branch pipeline is communicated with the chamber with the lowest water level height. According to the bioartificial liver supporting system, the liquid separation bottle is arranged, and the water level height difference of the multiple chambers formed in the liquid separation bottle is utilized, so that seed cells and cell debris contained in blood plasma are deposited, the situation that the seed cells and the cell debris are infused back into the body of a patient along with the blood plasma to cause discomfort of the patient is avoided, and the use safety of the bioartificial liver supporting system is improved.

Description

Technical Field

[0001] This application relates to the field of bioartificial livers, and particularly to a bioartificial liver support system. Background Art

[0002] Liver failure has an acute onset and a high mortality rate, which is a major problem that urgently needs to be solved at present. The most effective current treatment method is liver transplantation, but the shortage of donor livers limits the application of this treatment. As a new strategy for treating liver failure, artificial liver can gain time for liver failure patients, enabling the failing liver to regenerate or successfully transition to liver transplantation.

[0003] The pipeline of the bioartificial liver system is complex, involving multiple circulations, including blood circulation, plasma circulation, and bioreactor circulation. In the prior art, after the action of the bioreactor, cells and their debris in the reactor are likely to fall off and enter the plasma. After secondary plasma separation, the plasma containing cells and their debris often causes blockage of the filter membrane during re-circulation, resulting in an increase in pressure inside the reactor. Summary of the Invention

[0004] The purpose of this application is to provide a bioartificial liver support system containing a liquid separation bottle for removing seeded cells and their cell debris carried in the plasma.

[0005] To achieve the above purpose, this application provides the following technical solutions: A bioartificial liver support system includes at least the following sub-pipelines connected in sequence: a blood input sub-pipeline, a plasma separation sub-pipeline, a biological purification sub-pipeline, and a plasma return sub-pipeline. A liquid separation bottle is provided between the biological purification sub-pipeline and the plasma return sub-pipeline; The liquid separation bottle includes a bottle body. At least three partition plates are provided inside the bottle body, and the heights of the partition plates decrease sequentially along the circumferential direction to divide the inside of the bottle body into at least three chamber cavities with sequentially decreasing water level heights along the circumferential direction. The biological purification sub-pipeline is communicated with the chamber cavity with the highest water level height, and the plasma return sub-pipeline is communicated with the chamber cavity with the lowest water level height.

[0006] Further setting: Four partition plates with sequentially decreasing heights are provided inside the liquid separation bottle to divide the liquid separation bottle into four chamber cavities with sequentially decreasing water level heights, and the bottom areas of the four chamber cavities increase sequentially as the water level height decreases sequentially.

[0007] Further setting: The partition plate with the lowest height is provided with an upward opening, and a replaceable filter membrane is provided at the opening.

[0008] Further setting: An exhaust adjustment conduit is provided at the top of the bottle body, and a filter membrane is provided at the port of the exhaust adjustment conduit outside the bottle body.

[0009] Further settings: The biological purification branch pipeline includes a cell contact biological reactor, which includes an outer tank body and a reaction column arranged inside the outer tank body. The reaction column includes a reaction cavity defined by an annular column wall, and an inflow disc and an outflow disc respectively arranged at the bottom and top of the reaction cavity. A magnetic stirring mechanism is arranged at the bottom of the outer tank body.

[0010] Further settings: A top cover is arranged at the top of the outer tank body. A perfusion inflow conduit and a perfusion outflow conduit are penetrated through the top cover. The perfusion inflow conduit is connected to the plasma separation branch pipeline. The perfusion outflow conduit is connected to the liquid separation bottle and extends to the chamber with the highest water level in the liquid separation bottle. The ends of the perfusion inflow conduit and the perfusion outflow conduit located inside the outer tank body extend to the bottom of the outer tank body.

[0011] Further settings: An air vent conduit extending to the bottom of the outer tank body is also penetrated through the top cover.

[0012] Further settings: The plasma separation branch pipeline includes a plasma separator, which is provided with a blood inlet, a plasma outlet and a blood cell outlet. The blood inlet is connected to the blood input branch pipeline. The plasma outlet is connected to the perfusion inflow conduit. The blood cell outlet is connected to the plasma return branch pipeline.

[0013] Further settings: An adsorption branch pipeline including an adsorption column is arranged between the plasma separation branch pipeline and the biological purification branch pipeline. The adsorption column includes a resin adsorption column and / or a bilirubin adsorption column.

[0014] Further settings: Peristaltic pumps are arranged on the blood input branch pipeline, the plasma separation branch pipeline, the biological purification branch pipeline and the plasma return branch pipeline.

[0015] Compared with the prior art, the solution of the present application has the following advantages: In the bioartificial liver support system of the present application, by using the height difference of the water levels in the multiple chambers formed inside the liquid separation bottle connected after the cell contact biological reactor, the seed cells and cell debris contained in the plasma are deposited, avoiding the discomfort of the patient caused by the back-transfusion of the seed cells and their cell debris into the patient's body with the plasma, and improving the safety of the use of the bioartificial liver support system.

[0016] The additional aspects and advantages of the present application will be partially given in the following description, and these will become obvious from the following description, or will be understood through the practice of the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The above-mentioned and / or additional aspects and advantages of the present application will become obvious and easy to understand from the following description of the embodiments in conjunction with the drawings, where: Figure 1Schematic structural diagram of an embodiment of the bioartificial liver support system of the present application; Figure 2 Internal schematic diagram of the liquid separation bottle in the bioartificial liver support system of the present application; Figure 3 Schematic diagram of the partition structure of the liquid separation bottle in the bioartificial liver support system of the present application.

[0018] In the figure, 1 is the blood input sub-pipeline; 12 is the drug injector; 2 is the plasma separation sub-pipeline; 21 is the plasma separator; 3 is the biological purification sub-pipeline; 31 is the cell-contact biological reactor; 311 is the outer tank body; 312 is the top cover; 313 is the reaction column; 314 is the inflow tray; 315 is the outflow tray; 316 is the magnetic stirring device; 317 is the perfusion inflow catheter; 318 is the perfusion outflow catheter; 319 is the ventilation catheter; 4 is the return plasma sub-pipeline; 41 is the venous chamber; 5 is the liquid separation bottle; 51 is the bottle body; 52 is the bottle cap; 53 is the partition; 541 is the first chamber; 542 is the second chamber; 543 is the third chamber; 544 is the fourth chamber; 55 is the filter membrane; 56 is the exhaust adjustment catheter; 6 is the adsorption sub-pipeline; 61 is the resin adsorption column; 62 is the bilirubin adsorption column. Detailed implementation manners

[0019] The embodiments of the present application are described in detail below. The examples of the embodiments are shown in the drawings, in which the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described by referring to the drawings below are exemplary and are only used to explain the present application, and cannot be construed as a limitation to the present application.

[0020] In view of the problem that plasma containing cells and their debris can cause blockage of the filter membrane, the present application provides a bioartificial liver support system. Please refer to Figures 1 to 3 , which at least includes the following sub-pipelines connected in sequence: the blood input sub-pipeline 1, the plasma separation sub-pipeline 2, the biological purification sub-pipeline 3, the return plasma sub-pipeline 4, and the liquid separation bottle 5 provided between the biological purification sub-pipeline 3 and the return plasma sub-pipeline 4. Through the liquid separation bottle 5, the situation of filter membrane blockage caused by using a filter type plasma separator for plasma can be effectively prevented.

[0021] Specifically, the blood input sub-pipeline 1 includes a blood input end and a drug injector 12 connected in parallel to the blood input sub-pipeline 1. The drug injector 12 can select a syringe or the like to inject drugs into the blood input sub-pipeline 1 quantitatively or regularly. The drugs injected into the blood input sub-pipeline 1 can select anticoagulant drugs to prevent blood coagulation. The anticoagulant drugs can select one of heparin, hirudin, sodium citrate, potassium fluoride, and / or EDTA.

[0022] Blood is input into the bioartificial liver support system of the present application through the blood input branch pipeline 1, and then into the plasma separation branch pipeline 2. The plasma separation branch pipeline 2 includes a plasma separator 21. The plasma separator 21 includes a blood inlet, a plasma outlet, and a blood cell outlet. The blood inlet is connected to the blood input branch pipeline 1, the plasma outlet is connected to the biological purification branch pipeline 3, and the blood cell outlet is connected to the plasma return branch pipeline 4. Blood enters the plasma separator 21 through the blood inlet and is separated into plasma and blood cells. The plasma is output from the plasma outlet to the biological purification branch pipeline 3 for in vitro repair, and the blood cells flow out from the blood cell outlet to the plasma return branch pipeline 4 to return to the body in a timely manner.

[0023] The biological purification branch pipeline 3 includes a cell-contact biological reactor 31. The cell-contact biological reactor 31 includes an outer tank body 311, a top cover 312 covering the top of the outer tank body 311, and a reaction column 313 arranged inside the outer tank body 311. The reaction column 313 includes a reaction cavity defined by an annular column wall, an inflow disk 314, and an outflow disk 315. The inflow disk 314 covers the bottom of the reaction cavity, and the outflow disk 315 covers the top of the reaction cavity. A biological scaffold material is arranged inside the reaction column 313, and seed cells are inoculated on the biological scaffold material. The plasma separated from the plasma separation branch pipeline 2 flows into the biological purification branch pipeline 3, and the plasma makes full contact with the oxygen outside the reaction column 313 to provide oxygen for the seed cells inside the reaction column 313. The top cover 312 is also provided with a perfusion inflow conduit 317 and a perfusion outflow conduit 318. The perfusion inflow conduit 317 is connected to the plasma separation branch pipeline 2, and the perfusion outflow conduit 318 is connected to the liquid separation bottle 5. The ends of the perfusion inflow conduit 317 and the perfusion outflow conduit 318 located inside the outer tank body 311 both extend to the bottom of the outer tank body 311, and the end of the perfusion outflow conduit 318 is located above the end of the perfusion inflow conduit 317. The perfusion inflow conduit 317 extends to the bottom of the outer tank body 311 to facilitate the entry of plasma into the reaction column 313. The plasma flows from the outflow disk 315 at the top of the reaction column 313 into the internal space of the outer tank body 311 outside the reaction column 313. At this time, the plasma processed by the reaction column 313 will cover the unprocessed plasma and is transported to the liquid separation bottle 5 by the perfusion outflow conduit 318. A magnetic stirring device 316 is also arranged at the bottom of the outer tank body 311. The magnetic stirring device 316 can rotate to generate a liquid vortex, thereby providing power for the plasma, driving the plasma to enter the reaction column 313 through the inflow disk 314 at the top of the reaction column 313 and then flow out through the outflow disk 315. That is, under the drive of the magnetic stirring device 316, the plasma moves from the bottom to the top of the reaction column 313, which is conducive to the full contact between the plasma and the seed cells inside the reaction column 313, and then completes the detoxification, biosynthesis, and decomposition processes. At the same time, it can increase the plasma dissolved oxygen content and improve the volumetric efficiency. Finally, the plasma flows along the outer surface of the reaction column 313 to the bottom of the outer tank body 311 and is then transported to the liquid separation bottle 5 through the perfusion outflow conduit 318.

[0024] In addition, a ventilation conduit 319 extending into the interior of the outer tank body 311 is provided on the top cover 312. The ventilation conduit 319 extends to the bottom of the outer tank body 311 at the lower end of the outer tank body 311 to achieve sufficient oxygen dissolution in the plasma. The upper end of the ventilation conduit 319 outside the outer tank body 311 can be connected to an oxygen supply device to ensure stable oxygen supply conditions. The ventilation conduit 319 of the present application is also arranged away from the perfusion inflow conduit 317 and the perfusion outflow conduit 318 to prevent the bubbles formed when oxygen is introduced into the ventilation conduit 319 from directly entering the subsequent circulation, reducing the probability of forming pipeline air embolisms.

[0025] Furthermore, an adsorption branch pipeline 6 is provided between the plasma separation branch pipeline 2 and the biological purification branch pipeline 3. The adsorption branch pipeline 6 includes at least one adsorption column. The adsorption column can be a resin adsorption column 61 and / or a bilirubin adsorption column 62. The resin adsorption column 61 can non-selectively adsorb toxins and inflammatory mediators in the plasma, and the bilirubin adsorption column 62 can be used to adsorb bilirubin in the plasma. The adsorption branch pipeline 6 is used for pre-purifying the plasma to reduce impurities in the plasma, which is beneficial to maintaining the longer-term viability of the seed cells in the cell contact type bioreactor 31 and also beneficial to maintaining the good operation of the bioartificial liver support system.

[0026] The plasma processed by the cell contact type bioreactor 31 flows into the separation flask 5 through the perfusion outflow conduit 318. The separation flask 5 includes a flask body 51 and a bottle cap 52. At least three partition plates 53 are provided inside the flask body 51, and the heights of the partition plates 53 decrease sequentially in the circumferential direction to divide the interior of the flask body 51 into at least three chamber cavities with sequentially decreasing water levels in the circumferential direction. The biological purification branch pipeline 3 is communicated with the chamber cavity with the highest water level, and the return plasma branch pipeline 4 is communicated with the chamber cavity with the lowest water level. The plasma passing through the biological purification branch pipeline 3 is introduced into the chamber cavity with the highest water level of the separation flask 5 and then flows out from the chamber cavity with the highest water level of the separation flask 5 into the return plasma branch pipeline 4. The heavier cells and cell debris will deposit at the bottom of the chamber cavity. Then, using the water level difference, the seed cells and their cell debris in the plasma can be deposited in the chamber cavity with a higher water level, greatly reducing the content of seed cells and their cell debris in the plasma entering the chamber cavity with the lowest water level, so that the plasma flowing out into the return plasma branch pipeline 4 contains no or very few seed cells and their cell debris.

[0027] In a preferred embodiment, four partition plates 53 are provided. The heights of the four partition plates 53 decrease successively in the counterclockwise direction, so as to divide the interior of the liquid separation bottle 5 into four chamber cavities with water levels decreasing successively in the counterclockwise direction, which are respectively denoted as the first chamber cavity 541, the second chamber cavity 542, the third chamber cavity 543 and the fourth chamber cavity 544 in the order of decreasing water level. The first chamber cavity 541 and the fourth chamber cavity 544 are adjacently arranged, and the partition plate 53 between the first chamber cavity 541 and the fourth chamber cavity 544 is the partition plate 53 with the highest height. The bottom areas of the four chamber cavities correspondingly increase successively as the water levels decrease successively, that is, the chamber cavity with the highest water level (the first chamber cavity 541) has the smallest bottom area, and the chamber cavity with the lowest water level (the fourth chamber cavity 544) has the largest bottom area, thereby reducing the plasma content remaining in the chamber cavity.

[0028] Further, an upward opening is provided on the partition plate 53 (i.e., the partition plate with the lowest height) between the third chamber cavity 543 and the fourth chamber cavity 544. A filter membrane 55 for blocking cells and cell debris is inserted at the opening. The filter membrane 55 extends upward from the bottom of the bottle body 51 to a position equal to the height of the partition plate 53 with the highest height. An installation groove for inserting the filter membrane 55 is formed at the opening of the bottle body 51 and the partition plate 53. A rubber strip is arranged in the installation groove to ensure the sealing performance of the filter membrane 55 to separate the third chamber cavity 543 and the fourth chamber cavity 544. Plasma can pass through the filter membrane 55 at the opening of the partition plate 53 to flow from the third chamber cavity 543 into the fourth chamber cavity 544. Cells and cell debris are blocked by the filter membrane 55 and remain in the third chamber cavity 543. The plasma flows out of the liquid separation bottle 5 through the return plasma branch pipeline 4 communicating with the fourth chamber. Under the same air pressure, due to the fluidity of the liquid, the plasma in the third chamber cavity 543 will continuously pass through the filter membrane 55 and flow into the fourth chamber cavity, thereby further reducing the plasma remaining in the third chamber cavity.

[0029] An exhaust adjustment conduit 56 is provided at the top of the bottle body 51. A pinch valve (not shown) is provided in the middle of the exhaust adjustment conduit 56. The internal air pressure of the liquid separation bottle 5 is adjusted through the exhaust adjustment conduit 56. At the same time, a filter membrane (not shown) is provided at the port of the exhaust adjustment conduit 56 outside the bottle body 51. The setting of the filter membrane can prevent sundries from entering the liquid separation bottle 5 through the exhaust adjustment conduit 56.

[0030] The plasma that has passed through the liquid separation flask 5 enters the return plasma branch pipeline 4. The return plasma branch pipeline 4 includes a venous pot 41 that is connected to the blood cell outlet of the plasma separator 21 and is provided with a whole blood outlet. The upstream of the return plasma branch pipeline 4 is for flowing in the purified plasma, and its downstream is a blood output end connected to the recipient. The purified plasma and the blood cells separated from the plasma separator 21 can be mixed into whole blood at the venous pot 41, and then returned to the patient's body through the blood output end, thereby completing the biological purification of the plasma.

[0031] Further, a bubble monitor is provided at the output end of the venous pot 41 of the return plasma branch pipeline 4. After the whole blood mixed in the venous pot 41 is detected by the bubble monitor, it can ensure that the whole blood transfused into the patient's body does not contain bubbles, avoiding the problem of pipeline air embolism in the patient.

[0032] In addition, peristaltic pumps are provided on each of the blood input branch pipeline 1, plasma separation branch pipeline 2, biological purification branch pipeline 3, and return plasma branch pipeline 4. Under the power provided by each peristaltic pump, blood enters the plasma separation branch pipeline 2 from the blood input pipeline. The plasma separator 21 of the plasma separation branch pipeline 2 separates the blood into plasma and blood cells. Among them, the separated plasma flows out from the plasma outlet, and the separated blood cells flow out from the blood cell outlet. The outflowing plasma enters the adsorption branch pipeline 6 to preliminarily purify the plasma, and then flows out to the biological purification branch pipeline 3. In the biological purification branch pipeline 3, the cell contact type bioreactor 31 functions to detoxify, transform, synthesize, etc. the toxic plasma. The detoxified plasma then flows into the liquid separation flask 5. By the height difference of the water levels in each chamber of the liquid separation flask 5, the cells and cell debris contained in the plasma can be deposited in the chamber with a higher water level, effectively reducing the seeded cells and their cell debris carried in the plasma and avoiding the rejection reaction caused by the seeded cells and their cell debris being input into the patient's body with the plasma. The plasma after the cell deposition treatment in the liquid separation flask 5 enters the return plasma branch pipeline 4 and is mixed with the blood cells in the venous pot 41 to be transfused back into the patient's body together, thereby completing the whole process of blood biological purification.

[0033] In summary, the bioartificial liver support system of the present application completes the purification of blood based on the cell contact type bioreactor 31. The liquid separation flask 5 connected after the cell contact type bioreactor 31 can utilize the height difference of the water levels in multiple chambers formed inside it to deposit the seeded cells and cell debris contained in the plasma, avoiding the discomfort of the patient caused by the seeded cells and their cell debris being transfused back into the patient's body with the plasma, and improving the safety of the use of the bioartificial liver support system of the present application.

[0034] The above are only some embodiments of the present application. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present application, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present application.

Claims

1. A bioartificial liver support system, characterized in that: It at least includes the following sub-pipelines connected in sequence: a blood input sub-pipeline, a plasma separation sub-pipeline, a biological purification sub-pipeline, and a return plasma sub-pipeline. A liquid separation bottle is provided between the biological purification sub-pipeline and the return plasma sub-pipeline. The liquid separation bottle includes a bottle body. At least three partition plates are provided inside the bottle body. The heights of the partition plates decrease sequentially along the circumferential direction, so as to divide the inside of the bottle body into at least three chamber cavities with sequentially decreasing water levels along the circumferential direction. The biological purification sub-pipeline is communicated with the chamber cavity with the highest water level, and the return plasma sub-pipeline is communicated with the chamber cavity with the lowest water level.

2. The bioartificial liver support system according to claim 1, wherein: Four partition plates with sequentially decreasing heights are arranged in the liquid separation bottle to divide the liquid separation bottle into four chamber cavities with sequentially decreasing water levels, and the bottom areas of the four chamber cavities increase sequentially as the water levels decrease sequentially.

3. The bioartificial liver support system according to claim 2, wherein: The partition plate with the lowest height is provided with an upward opening, and a replaceable filter membrane is provided at the opening.

4. The bioartificial liver support system according to claim 1, characterized in that: An exhaust adjustment conduit is provided at the top of the bottle body, and a filter membrane is provided at the port of the exhaust adjustment conduit located outside the bottle body.

5. The bioartificial liver support system according to claim 1, wherein: The biological purification sub-pipeline includes a cell-contact biological reactor. The cell-contact biological reactor includes an outer tank body and a reaction column arranged inside the outer tank body. The reaction column includes a reaction cavity defined by an annular column wall, and an inflow disk and an outflow disk respectively arranged at the bottom and top of the reaction cavity. A magnetic stirring mechanism is provided at the bottom of the outer tank body.

6. The bioartificial liver support system according to claim 5, characterized in that: A top cover is provided at the top of the outer tank body. A perfusion inflow conduit and a perfusion outflow conduit are penetrated through the top cover. The perfusion inflow conduit is connected to the plasma separation sub-pipeline, the perfusion outflow conduit is connected to the liquid separation bottle and extends to the chamber cavity with the highest water level in the liquid separation bottle, and the ends of the perfusion inflow conduit and the perfusion outflow conduit located inside the outer tank body extend to the bottom of the outer tank body.

7. The bioartificial liver support system according to claim 6, wherein: An air vent conduit extending to the bottom of the outer tank body is also penetrated through the top cover.

8. The bioartificial liver support system according to claim 6, characterized in that: The plasma separation sub-pipeline includes a plasma separator. The plasma separator is provided with a blood inlet, a plasma outlet, and a blood cell outlet. The blood inlet is connected to the blood input sub-pipeline, the plasma outlet is connected to the perfusion inflow conduit, and the blood cell outlet is connected to the return plasma sub-pipeline.

9. The bioartificial liver support system according to claim 8, wherein: An adsorption sub-pipeline including an adsorption column is provided between the plasma separation sub-pipeline and the biological purification sub-pipeline. The adsorption column includes a resin adsorption column and / or a bilirubin adsorption column.

10. The bioartificial liver support system according to claim 1, characterized in that: Peristaltic pumps are provided on the blood input sub-pipeline, the plasma separation sub-pipeline, the biological purification sub-pipeline, and the return plasma sub-pipeline.

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