CN101732770B - Dual-cavity liquid storage tank for biological artificial liver support system - Google Patents

Dual-cavity liquid storage tank for biological artificial liver support system Download PDF

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CN101732770B
CN101732770B CN200910155039XA CN200910155039A CN101732770B CN 101732770 B CN101732770 B CN 101732770B CN 200910155039X A CN200910155039X A CN 200910155039XA CN 200910155039 A CN200910155039 A CN 200910155039A CN 101732770 B CN101732770 B CN 101732770B
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storage tank
cavity
liquid storage
dual
support system
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CN101732770A (en
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李兰娟
赵立夫
张安业
吕国良
朱春侠
陈佳佳
潘小平
章益民
喻成波
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Zhejiang University ZJU
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Abstract

The invention discloses a dual-cavity liquid storage tank for a biological artificial liver support system. The dual-cavity liquid storage tank comprises an inner cavity and an outer cavity, wherein the top of the outer cavity is provided with a first liquid inlet and a first air pressure balance hole; the top of the inner cavity is provided with a second liquid inlet and a second air pressure balance hole; the bottom of the inner cavity is provided with a first liquid outlet; the side wall, which is close to the bottom, of the inner cavity is provided with a second liquid outlet; the second liquid outlet passes through the outer cavity by means of a pipelike passage, and directly leads to the outside of the dual-cavity liquid storage tank from the inner cavity; and the pipelike passage is provided with a plurality of outer cavity side holes on the partial side wall of the outer cavity. The dual-cavity liquid storage tank for the biological artificial liver support system realizes that severe hepatitis plasma flows through a bioreactor for multiple times to form a high-efficiency circulation path, thereby playing better therapeutic effect. The proportion of volume sizes of the inner cavity and the outer cavity of the dual-cavity liquid storage tank for the biological artificial liver support system can also be reset according to clinical concrete practical requirements, and is expanded or reduced so as to be applied to clinic treatment more reasonably.

Description

Dual-cavity liquid storage tank for biological artificial liver support system
Technical field
The invention belongs to field of biomedicine technology, relate to a kind of armarium, relate in particular to a kind of bioartificial liver's of being applied to treatment, can effectively improve the important device of bioartificial liver's therapeutic effect: dual-cavity liquid storage tank for biological artificial liver support system.
Background technology
Current, the liver failure state of an illness is critical, progress rapidly, case fatality rate is high, is global problem to the treatment of liver failure always.And artificial liver treatment has at present become irreplaceable treatment means of hepatitis gravis liver failure; Especially the repertoire that the bioartificial liver in theory can compensatory liver; Representing the trend of artificial liver from now on; Be faced with huge clinical demand, have potential applicability in clinical practice widely.Bioartificial liver's ultimate principle be patient's blood or plasma flow through being loaded with the bioreactor of biological activity cell, in this process, the biological activity cell is accomplished the metabolism of blood (blood plasma) toxic material on the one hand; Simultaneously its synthetic bioactive substance is released into blood; Environment is disorderly in correcting, and temporarily substitutes the partial function of depleted liver, for winning chance from recovery of body liver or liver transplantation; Thereby the reduction mortality reaches therapeutic purposes.
Be understood that; Bioartificial liver's curative effect is in depending on reaction vessel hepatocellular quantity and the biological function; Mass exchange efficient between blood samples of patients (blood plasma) and the cultured cell in vitro also becomes the key factor that affects the treatment, and liquid storage tank reasonable in design plays pivotal role in this link.External bioartificial liver devices of having carried out I-III phase clinical verification has BLSS, AMC-BAL, ELAD, MELS, HepatAssist etc., does not reach the clinical efficacy of expection more.Trace it to its cause, though a very important aspect is that they are conceived to pair cell source and reaction vessel Study on Characterization, study this assembly of liquid storage tank fully.The artificial liver device that lacks liquid storage tank causes blood samples of patients (blood plasma) through once promptly returning in the body after the circulation, and this makes blood samples of patients (blood plasma) and iuntercellular lack sufficient mass exchange, and bioartificial liver's therapeutic efficiency is low.Most artificial liver devices have been equipped with liquid storage tank, are single cavity configuration mostly, although can realize repeatedly circulating, the defective of its structure can't avoid the not flowing through intravital situation of blood (blood plasma) direct feedback of reaction vessel promptly forms so-called invalid circulation.
Summary of the invention
The objective of the invention is to deficiency to prior art; A kind of dual-cavity liquid storage tank for biological artificial liver support system is provided, and the present invention is applicable to that the bioartificial liver treats, and can starch the bioreactor of repeatedly flowing through with weighing liver blood; Form the efficient circulation path, play better therapeutic effect.
The objective of the invention is to realize through following technical scheme: a kind of dual-cavity liquid storage tank for biological artificial liver support system comprises inner chamber and exocoel; Wherein, Outer top of chamber is provided with first liquid-inlet and first air equalizer opening, and interior top of chamber is provided with second liquid-inlet and second air equalizer opening, and intracavity bottom is provided with first liquid outlet; Intracavity sidewall is provided with second liquid outlet near the bottom; This second liquid outlet, is directly led to outside the dual-cavity liquid storage tank by inner chamber by way of exocoel by a tubular conduit, and this tubular conduit sidewall of cavity segment outside is provided with several exocoel side openings.
Further, said inner chamber and exocoel are made up of the concentric hollow cylinder such as height such as grade of two tops and bottom seals, and material is plastics or lucite.
Further, the radius of said first air equalizer opening and second air equalizer opening is 0.3cm, establishes filter membrane in all.
Further, said filter membrane is thick to be 0.22 micron, and its material is a mixed cellulose ester.
Further, said exocoel side opening 7 has three, and diameter is 0.15cm.
The invention has the beneficial effects as follows that dual-cavity liquid storage tank for biological artificial liver support system of the present invention has been realized the heavy liver blood slurry bioreactor of repeatedly flowing through, and forms the efficient circulation path, thereby can give play to better therapeutic effect.Dual-cavity liquid storage tank for biological artificial liver support system provided by the invention also can specifically be put into practice requirement according to clinical, and inside and outside two-chamber volume size ratio is reset, and enlarges or dwindles, thereby more reasonably be applied to clinical.
Description of drawings
Fig. 1 is the perspective view of biological artificial liver support system with dual-cavity liquid storage tank;
Fig. 2 for biological artificial liver support system with the external system supplymentary schematic representation of apparatus of dual-cavity liquid storage tank.
The specific embodiment
Describe the present invention in detail according to accompanying drawing below, it is more obvious that the object of the invention and effect will become.
As shown in Figure 1; Dual-cavity liquid storage tank for biological artificial liver support system of the present invention such as comprises with one heart at high inner chamber 8 and exocoel 9, first liquid-inlet 1, second liquid-inlet 2, first air equalizer opening 4, second air equalizer opening 3, first liquid outlet 5, second liquid outlet 6, exocoel side opening 7.The overall external form of liquid storage tank is made up of two high cylinders such as concentric, correspondingly in the pond is divided into airtight inside and outside two-chamber.First liquid-inlet 1 of liquid storage tank upper top and first air equalizer opening, 4 equal communication with cavity 8, the second liquid-inlets 2 and second air equalizer opening 3 all are communicated with exocoel 9.First air equalizer opening 4 and second air equalizer opening 3 are communicated with outside inner chamber 8, exocoel 9 and the pond respectively; Keep the inside and outside atmospheric pressure balance in pond; And air equalizer opening all is provided with 0.22 micron filter membrane in the hole, guarantees aseptic condition in the pond, and filter membrane material can be mixed cellulose ester etc.
The liquid storage tank lower bottom part has first liquid outlet 5, as purifying the path that back blood plasma returns human body.Sidewall is near lower bottom part first liquid outlet 6, and this outlet, directly led to outside the liquid storage tank by inner chamber 8, and the sidewall of these passage exocoel 9 parts is provided with several exocoel side openings 7 by way of exocoel 9 by a tubular conduit, and the about 0.15cm of diameter among the figure is 3.
Exocoel 9 will hold the heavy liver blood slurry from human body by first liquid-inlet 1, inner chamber 8 then by second liquid-inlet 2 hold with the bioreactor effect after purification blood plasma.First liquid-inlet 1 connects the pipeline of plasma separator 10, is driven by pump, and cracked ends first liquid-inlet 1 does not pump into heavy liver blood slurry in liquid storage tank exocoel 9; 2 of second liquid-inlets connect the pipelines of bioreactor 11, and heavy liver blood slurry and part circulation blood plasma are driven by pump after in bioreactor 11, interacting with hepatocyte, and blood plasma returns liquid storage tank inner chamber 8 after second liquid-inlet 2 is as purification.This liquid storage tank upper top has two place's air equalizer openings; Pore radius is about 0.3cm, is communicated with outside inner chamber 8, exocoel 9 and the pond respectively, thereby keeps the inside and outside atmospheric pressure balance in pond; And this two places air equalizer opening is provided with 0.22 micron filter membrane in the hole, thereby can keep aseptic condition in the liquid storage tank.The liquid storage tank lower bottom part has first liquid outlet 5, connects inner chamber 8, and outwards connects the blood plasma pipeline that returns human body.Blood plasma after part purifies in the liquid storage tank inner chamber 8 can return human body through first liquid outlet 5.Wherein, by the heavy liver plasma volume of first liquid-inlet, 1 entering exocoel 9, with impartial by the plasma volume maintenance of first liquid outlet 5 after inner chamber 8 effusive purifications.The liquid storage tank sidewall has second liquid outlet 6 near lower bottom part; This liquid outlet 6 directly led to outside the liquid storage tank by inner chamber 8, and the sidewall of these passage approach exocoel 9 parts is provided with exocoel side opening 7 by a tubular conduit; Establish 3 holes altogether, the about 0.15cm of the diameter in every hole.Second liquid outlet 6 will be communicated with the pipeline of bioreactor; Driven by pump, blood plasma will get into the pipeline of bioreactors through second liquid outlet 6 after the purification of inner chamber 8, and the heavy liver blood slurry of exocoel 9 will be mixed by the blood plasma of suction after liquid outlet 6 and inner chamber 8 purifications by exocoel side opening 7 mutually; Get into bioreactor 11 in the lump; After interacting with hepatocyte in the bioreactor 11,, form once circulation after second liquid-inlet 2 returns inner chamber 8.The caliber setting of above liquid-inlet and liquid outlet is the about 0.6cm of diameter of every pipe, and in addition, the length of liquid storage tank exterior portions is 1.5cm.
Dual-cavity liquid storage tank for biological artificial liver support system provided by the invention; Form by inside and outside two-chamber, by means of second liquid outlet 6 and exocoel side opening 7, under the drive of pump; Can draw the blood plasma of inside and outside two-chamber simultaneously; And can form repeatedly effectively that the bioartificial liver treats circulation, avoided heavy liver blood slurry to react with hepatocyte and directly returned in the body, thereby brought into play bioartificial liver's therapeutical effect more efficiently without bioreactor.
The sheathing material of this instance dual-cavity liquid storage tank for biological artificial liver support system can be plastics or lucite, and size dimension is: liquid storage tank inner chamber 8 radiuses are 3cm, and exocoel 9 radiuses are 4cm; All remove wall thickness; The pond height is 9cm, the about 250ml of inner chamber 8 volumes, the about 200ml of exocoel 9 volumes.Can or dwindle according to the amplification of clinical practice needs during actual fabrication, make best size.
As shown in Figure 2: heavy hepatic blood is extracted out by pump from venous patient, gets into plasma separator 10, and heavy hepatic blood separates into attach most importance to liver blood slurry and hemocyte, and heavy liver blood slurry will be got in the exocoel 9 of liquid storage tank 12 by first liquid-inlet 1.Because the swabbing action of pump in the biological reaction vessel path outside the pond; Heavy liver blood slurry in the exocoel 9 will be through the exocoel side opening 7 of second liquid outlet 6 at exocoel 9 part passages; Flow out entering through second liquid outlet 6 and be equipped with in the hepatocellular bioreactor 11, interact with hepatocyte.Blood plasma after carrying out interacting for the first time is as purifying the inner chamber 8 that blood plasma will get into liquid storage tank 12 through first liquid-inlet 2; With in the inner chamber 8 the plasma substitute of preliminary filling mix each other; Purification blood plasma major part after the dilution will be driven by pump once more through second liquid outlet 6 and get into bioreactor 11 and hepatocyte interaction, form the circulation that heavy liver blood slurry repeated multiple times gets into bioreactor 11.The purification blood plasma that living through repeatedly circulates gets into after bioreactor 11 fully acts on will be driven by pump by first liquid outlet 5, and the pipeline of human body is returned in entering, and finally with after hemocyte mixes each other returns human body.
The present invention uses dual-cavity liquid storage tank for biological artificial liver support system, compares with the ordinary cycle liquid storage tank, and huge advantage is arranged.Common liquid storage tank only is one the airtight three-dimensional bottle of several liquid access ways to be arranged; After heavy liver blood slurry gets into common liquid storage tank, can not isolate each other with the blood plasma after purifying, but be blended directly in together; Blood plasma after partially mixed will directly return human body; Thereby caused partly heavy liver blood slurry to interact, promptly directly returned in the body, do not had bioartificial liver's therapeutic effect without bioreactor and hepatocyte.And dual-cavity liquid storage tank for biological artificial liver support system provided by the present invention is made up of inside and outside two-chamber, and exocoel holds heavy liver blood slurry, and inner chamber holds the blood plasma after the purification, has guaranteed effective isolation of two parts blood plasma.Simultaneously; This liquid storage tank under the drive of pump, can be drawn the blood plasma of inside and outside two-chamber by means of the liquid outlet and the exocoel side opening of special setting simultaneously; And because the outside swabbing action of pump; Heavy liver blood slurry in the exocoel will be in inner chamber purify after blood plasma aspirate the entering bioreactor, and can inwardly directly not get into inner chamber, thereby effectively having avoided heavy liver blood to starch reacting without bioreactor and hepatocyte returns in the body directly.And the repeatedly effective bioartificial liver of the continuous formation of heavy liver blood slurry of blood plasma after purifying in the inner chamber and part exocoel treats circulation, brings into play bioartificial liver's therapeutic effect more efficiently.In addition; Compare with common liquid storage tank; The present invention solves pond inside and outside air pressure balance problem in the lump effectively and keeps the aseptic condition in the pond also through being provided with the air equalizer opening of 0.22 micron filter membrane, thereby is embodying special advantages aspect Pneumatic pressure power and the bio-safety.
This dual-cavity liquid storage tank for biological artificial liver support system through the structure of uniqueness, can effectively improve bioartificial liver's therapeutic efficiency, and reasonable in design, complete function, and the suitability is strong, has wide range of applications, and has good application prospects.

Claims (5)

1. a dual-cavity liquid storage tank for biological artificial liver support system is characterized in that, comprises inner chamber (8) and exocoel (9); Wherein, Exocoel (9) top is provided with first liquid-inlet (1) and first air equalizer opening (4); Inner chamber (8) top is provided with second liquid-inlet (2) and second air equalizer opening (3); Inner chamber (8) bottom is provided with first liquid outlet (5), and inner chamber (8) sidewall is provided with second liquid outlet (6) near the bottom, this second liquid outlet (6) by a tubular conduit by way of exocoel (9); Directly led to outside the dual-cavity liquid storage tank by inner chamber (8), the sidewall of this tubular conduit exocoel (9) part is provided with several exocoel side openings (7).
2. according to the said dual-cavity liquid storage tank for biological artificial liver support system of claim 1, it is characterized in that said inner chamber (8) and exocoel (9) are made up of the concentric hollow cylinder such as height such as grade of two tops and bottom seals, material is plastics.
3. according to the said dual-cavity liquid storage tank for biological artificial liver support system of claim 1, it is characterized in that the radius of said first air equalizer opening (4) and second air equalizer opening (3) is 0.3cm, establish filter membrane in all.
4. according to the said dual-cavity liquid storage tank for biological artificial liver support system of claim 3, it is characterized in that, thick about 0.22 micron of said filter membrane, its material is a mixed cellulose ester.
5. according to the said dual-cavity liquid storage tank for biological artificial liver support system of claim 1, it is characterized in that said exocoel side opening (7) has three, diameter is 0.15cm.
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Publication number Priority date Publication date Assignee Title
CN101966352B (en) * 2010-09-10 2013-03-13 浙江大学 Bioartificial liver support system and combined type liquid storage tank thereof
CN102210892B (en) * 2011-05-05 2012-12-19 浙江大学 Integrated microcapsule suspension fluidized bed bioreactor
CN103263706A (en) * 2013-05-09 2013-08-28 浙江大学 Plasma storage bag special for plasma exchange, absorption, and filtration treatment
CN105233382A (en) * 2015-11-04 2016-01-13 傅守勇 Medical anesthetic waste gas receiving device
CN106075625A (en) * 2016-08-26 2016-11-09 合肥市力维生物科技有限公司 A kind of Biotype artificial liver
CN107012090A (en) * 2017-03-09 2017-08-04 刘兴 A kind of external liver system
CN108072755A (en) * 2017-12-15 2018-05-25 重庆晓微城企业孵化器有限公司 Cultivation liquid storage organization in biosensor
CN108030968B (en) * 2018-01-15 2023-12-26 上海赛立维生物科技有限公司 Liquid storage tank for bioartificial liver support system

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CN1292713A (en) * 1998-01-20 2001-04-25 米特拉医疗技术公司 Apparatus for use in connection with removal of elements, especially exogenous antibodies, from blood or plasma
CN1631337A (en) * 2004-12-24 2005-06-29 浙江大学 Apparatus adapted for artificial liver
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Assignee: Weihai Weigao Life Science & Technology Co., Ltd.

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Denomination of invention: Dual-cavity liquid storage tank for biological artificial liver support system

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