CN101455864B - Mixed biology artificial liver vitro supporting device - Google Patents

Mixed biology artificial liver vitro supporting device Download PDF

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Publication number
CN101455864B
CN101455864B CN 200810243330 CN200810243330A CN101455864B CN 101455864 B CN101455864 B CN 101455864B CN 200810243330 CN200810243330 CN 200810243330 CN 200810243330 A CN200810243330 A CN 200810243330A CN 101455864 B CN101455864 B CN 101455864B
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pump
blood
end connects
plasma
artificial liver
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CN 200810243330
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CN101455864A (en
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丁义涛
施晓雷
褚薛慧
顾劲扬
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Nanjing Drum Tower Hospital
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Nanjing Drum Tower Hospital
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Abstract

The invention relates to an in vitro supporting device for a mixed biological artificial liver temporarily replacing the liver function of human body. The structure of the in vitro supporting device for the mixed biological artificial liver is as follows: a bioreactor in an incubator is connected with a reactor circulating pump and a membrane lung which is connected with an exchange column; the exchange column is connected with the reactor circulating pump; a blood pump is connected with a blood inlet and a separation tube; a blood plasma infusion pump is connected with a tee joint and an active carbon absorption column; a biological artificial liver pump is connected with the active carbon adsorption column and the exchange column; a dialysis pump is connected with the exchange column and a dialysis tube; the separation tube is connected with a blood pool and the tee joint which is connected with a discarded blood plasma reservoir and the blood plasma infusion pump; the active carbon adsorption column is connected with the artificial liver pump; the dialysis pump is connected with the blood pool, a dialyzate bag and a waste fluid reservoir; and the blood pool is connected with a blood outlet. The in vitro supporting device for the mixed biological artificial liver solves the respective defects of a non-biological artificial liver and a biological artificial liver, organically combines the non-biological artificial live and the biological artificial liver to generate synergistic reaction, and achieves the aims of plasma exchange, plasma infusion, biological artificial liver dialysis and hemodialysis.

Description

Mixed biology artificial liver vitro supporting device
Technical field
The present invention relates to a kind of armarium, particularly a kind of temporary transient mixed biology artificial liver vitro supporting device that substitutes human liver's function.
Background technology
The artificial liver device can be the patient of short duration liver function support is provided, and is effective auxiliary treatment means of diseases such as present liver failure, has a good application prospect.
Before the present invention, the artificial liver device mainly is divided into abiotic artificial liver and bioartificial liver's two big classes.
Abiotic artificial liver develop at present comparative maturity, its artificial liver device commonly used has following several kinds: plasmapheresis, blood plasma perfusion absorption, hemodialysis and hemofiltration device etc.The plasmapheresis device is through the separating plasma technology; Cell component in the blood samples of patients and plasma fraction are separated; With the latter with the displacement of human normal plasma or plasma substitute, thereby remove the liver toxic component in the blood plasma in patient's body that declines, its shortcoming is expensive and is prone to cause the blood plasma waste.The blood plasma device for casting is meant blood plasma through extracorporeal circulation; Be incorporated in the container that adsorbent (resin or active carbon) is housed; With some endogenous of adsorption removal or exogenous poisonous substance, like bilirubin etc., its shortcoming is that adsorption process does not have selectivity; When removing toxicant, a lot of useful active component in the blood plasma also is adsorbed.Haemodialysis equipment be with blood and dialysis solution in the semipermeable membrane both sides mode through disperse carry out mass exchange; Thereby remove the liver micromolecular material in some that declines in patient's body; Like carbamide, creatinine etc., regulate water balance through the mode of ultrafiltration simultaneously, stable interior environment; But this device can only be removed the liver part toxin in patient's body that declines, and is invalid to some macromolecular substances.
Though above-mentioned various abiotic artificial liver can be removed toxin to a certain extent, all can not replenish needed various active substances in patient's body constantly, can't accomplish the function and the effect of artificial liver device truly.
The appearance of bioartificial liver devices has remedied this defective.Bioartificial liver devices mainly is through in reaction vessel, cultivating the external source hepatocyte of high vigor, simulating the device of liver function in the normal human.Bioartificial liver devices also has multiple biological functions such as synthetic, metabolism, conversion except function of detoxification, can realize liver replacement therapy truly, but the technology of bioartificial liver devices is still immature at present, also is in the exploratory stage.And, if the decline toxin and the hepatocyte in metabolite and the bioreactor of a large amount of accumulation in patient's body of liver are directly carried out mass exchange, probably can cause the rapid forfeiture of hepatocyte activity and function, influence the performance of bio-artificial liver function.
Summary of the invention
The object of the invention just is to overcome the defective that above-mentioned abiotic artificial liver and bioartificial liver exist separately, designs, develops a kind of mixed biology artificial liver vitro supporting device.
Technical scheme of the present invention is:
Mixed biology artificial liver vitro supporting device; Upper left quarter is the incubator control knob in the shell, and upper right quarter is an incubator, and its major technique is characterised in that bioreactor is set in the incubator; Bioreactor one end coupled reaction device circulating pump; The other end connects membrane lung, and the membrane lung other end connects exchange column, exchange column other end coupled reaction device circulating pump; The shell mid portion is provided with blood pump, and its front pump one end connects the blood inlet, and the other end connects separator tube; Plasma perfusion pump one end connects threeway; The other end connects active carbon adsorption column, and bioartificial liver's pump one end connects active carbon adsorption column, and the other end connects exchange column; Dialysate pump one end connects exchange column, and the other end connects Dialysis tubing; The bottom is provided with heparin pump in the shell; The separator tube other end connects blood pool, and the blood pool other end connects threeway, and threeway two ends in addition connects discarded blood plasma jar, plasma perfusion pump respectively; Active carbon adsorption column one end connects the plasma perfusion pump, and the other end connects bioartificial liver's pump; Dialysis tubing one end connects dialysate pump, and the other end connects blood pool, two side openings on the Dialysis tubing; Wherein a side opening connects dialyzate bag; Another side opening connects discarded flow container, and blood pool one end connects plasma bags, separating plasma pipe and Dialysis tubing, and the blood pool other end connects the blood outlet.
Advantage of the present invention and effect are organic and dexterously abiotic artificial liver device and bioartificial liver devices are combined; Avoid the two defective separately; Make it to bring into play the advantage of abiotic artificial liver device; Bring into play the advantage of artificial liver device again, and make the two performance synergism that combines; Simultaneously, the combination of the two makes bioartificial liver devices obtain practical application.
Mixed biology artificial liver vitro supporting device of the present invention has simple in structure, reliable, is easy to realize, and is easy to operate.
Advantage of the present invention is specific as follows:
1, modes such as plasmapheresis, plasma perfusion, bioartificial liver, hemodialysis is integrated into a machine.
When 2, mixed biology artificial liver combination is used, at first carry out preliminary detoxifcation, avoided in the blood plasma noxious substance hepatocellular toxic action among the bioartificial liver of back through plasmapheresis and plasma perfusion.
When 3, mixed biology artificial liver combination was used, functions such as the secretion through the bioartificial liver, synthetic, metabolism had been replenished the useful active component that is lost by the front activated carbon adsorption in the blood plasma.
When 4, the mixed biology artificial liver combination was used, last hemodialysis had guaranteed blood behind the various artificial liver devices through the front, still can keep good fluid and electrolyte balance to get back in the human body, and can further remove small-molecule substances such as carbamide and creatinine.
5, be provided with membrane lung in the bioartificial liver loop that the present invention adopted, and in culture fluid, added erythrocyte, solve hepatocellular oxygen confession problem in the reaction vessel thereby take oxygen through erythrocyte.
Other advantage of the present invention and effect will continue explanation below.
Description of drawings
Fig. 1---structural principle sketch map of the present invention.
The right view of Fig. 2---Fig. 1.
The left view of Fig. 3---Fig. 1.
The specific embodiment
Brief summary of the invention of the present invention is following:
1. plasmapheresis: the plasmapheresis parts comprise front pump, heparin pump, plasma separator, plasma bags, discarded blood plasma jar and blood pool, and the plasmapheresis parts are positioned at before the plasma perfusion parts.Blood directly abandons after telling blood plasma through plasma separator, and fresh plasma is replenished by the plasma bags synchronous same-speed.Remove the part noxious substance through plasmapheresis.
2. plasma perfusion: the plasma perfusion parts comprise hemoperfusion pump and bilirubin adsorption column, and active carbon is housed in the adsorption column, and the plasma perfusion parts are positioned at after the plasmapheresis parts, before bioartificial liver's parts.The blood plasma of being told by plasma separator adsorbs to fall bilirubin etc. through active carbon adsorption column.
3. bioartificial liver: bioartificial liver's parts comprise bioartificial liver's pump, bioreactor pump, membrane lung, bioreactor and exchange column.These elements are formed loops, are positioned at after the plasma perfusion parts, before the hemodialysis parts, and place the constant incubator of 37 ℃ and 5%CO2, to keep the best living environment of hepatocyte in it.Circulation has culture fluid in this loop, is mixed with erythrocyte in the culture fluid, carries out oxygenate during through membrane lung, and takes oxygen to hepatocyte, thereby guarantee that oxygen supplies.Culture fluid in this loop and the blood plasma in the blood circuit constitute two circulations, in exchange column, carry out mass exchange, thereby have avoided immunoreactive generation.And through mass exchange, the toxic component in the blood plasma gets into reaction vessel, by the hepatocyte metabolism; And the excretory active substance of hepatocyte gets into blood plasma, and additional plasma perfusion adsorbs the active component that falls.
4. hemodialysis: the hemodialysis parts comprise dialysate pump, Dialysis tubing, dialyzate bag and discarded liquid bag, and the hemodialysis parts are positioned at after bioartificial liver's parts.Blood plasma is further removed small-molecule substances such as carbamide, creatinine in Dialysis tubing, and after regulating water-electrolyte balance, returns in patient's body.
Be practical implementation content of the present invention below:
Like Fig. 1, Fig. 2, shown in Figure 3:
Upper left quarter in shell 21 of the present invention is a control knob 22, the temperature in the control upper right quarter incubator 23, oxygen concentration, gas concentration lwevel etc.; In the incubator 23 of upper right quarter, be provided with bioreactor 11; Bioreactor 11 1 end coupled reaction device circulating pumps 12; The other end connects membrane lung 10, and membrane lung 10 other ends connect exchange column 9, and exchange column 9 is also distinguished coupled reaction device circulating pump 12, dialysate pump 13, bioartificial liver's pump 8; Mid portion is provided with blood pump in the shell 21, and wherein front pump 2 one ends connect blood inlet 1, and the other end connects separator tube 4, and separator tube 4 two ends in addition connects blood pool 17, threeway 5 respectively, and threeway 5 two ends in addition connects discarded blood plasma jar 18, plasma perfusion pump 6 respectively; Plasma perfusion pump 6 other ends connect active carbon adsorption column 7, and active carbon adsorption column 7 other ends connect bioartificial liver's pump 8, and dialysate pump 13 other ends connect Dialysis tubing 14; The bottom is provided with heparin pump 3 in the shell 21, and Dialysis tubing 14 other ends connect blood pool 17, two side openings on the Dialysis tubing 14, and one of them side opening connects dialyzate bag 16, and another side opening connects discarded flow container 19; Blood pool 17 connects plasma bags 15, separator tube 4, Dialysis tubing 14 and blood outlet 20 respectively.
Concrete application of the present invention:
1, part plasmapheresis
Before using threeway 5 is threaded to the 5a position.Blood is pumped into through front pump 2 by blood inlet 1, after heparin pump 3 heparinizations, gets into separator tube 4, and isolated blood plasma gets into discarded blood plasma jar 18 through threeway 5 backs; Fresh plasma gets into blood pool 17 by plasma bags 15 synchronous same-speeds, after separator tube 4 isolated erythrocyte mix, gets back in the body through blood outlet 20.In this course, fresh plasma replenishes speed and poisonous blood plasma, and to abandon speed identical, reaches through plasmapheresis and remove part noxious substance purpose.
2, plasma perfusion:
After part plasmapheresis step finishes, continue separated plasma, plasma perfusion pump 6 falls bilirubin etc. with isolating blood plasma through active carbon adsorption column 7 absorption with in the blood plasma pump people active carbon adsorption column 7, further removes the noxious substance in the blood plasma.
3, bioartificial liver:
Blood plasma is after active carbon adsorption column 7 detoxifcations; Get into bioartificial liver devices; In exchange column 9 with bioreactor 11 in the excretory active substance of hepatocyte carry out mass exchange; Accomplish hepatocellular secretion, metabolism, function such as synthetic, thereby replenish the active component that is adsorbed in the plasma perfusion step.
4, hemodialysis:
Blood plasma gets into Dialysis tubing 14 dialysis through behind the bioartificial liver, further removes small-molecule substances such as carbamide, creatinine, and regulates water-electrolyte balance, thereby guarantee the stable of patient's homeostasis.Blood plasma mixes with erythrocyte through behind the Dialysis tubing 14, gets back in patient's body through blood outlet 20.
The concrete steps in the 2nd~4 step are:
Threeway 5 is threaded to the 5b position.Blood is pumped into through front pump 2 by blood inlet 1; After heparin pump 3 heparinizations, get into separator tube 4, isolated blood plasma then gets into plasma perfusion pump 6 through threeway 5 backs, is pumped to active carbon adsorption column 7; Behind adsorpting detoxication by bioartificial liver's pump 8 pumps to exchange column 9; Culture fluid in the bioreactor 11 is pumped into exchange column 9 by reactor cycles pump 12 behind membrane lung 10 oxygenates, both carry out mass exchange in exchange column 9 after, blood plasma flow out by exchange column 9 and by dialysate pump 13 pumps to Dialysis tubing 14; Fresh dialysis fluid gets into Dialysis tubing 14 by bag filter 16, and the waste liquid after the dialysis then enters into discarded flow container 19; Blood plasma gets into blood pool 17 after dialysing, after isolated erythrocyte mixes, get back in the body through blood outlet 20.
Among the present invention, increase an exchange column 9 in the bioartificial liver loop, thereby carry out mass exchange, avoided immunoreactive generation through bicirculating mode.
Hence one can see that, and the present invention organically combines abiotic artificial liver and bioartificial liver devices, produces synergism, obtains good effect.

Claims (2)

1. mixed biology artificial liver vitro supporting device; Upper left quarter is the incubator control knob in the shell, and upper right quarter is an incubator, it is characterized in that being provided with in the incubator bioreactor; Bioreactor one end coupled reaction device circulating pump; The other end connects membrane lung, and the membrane lung other end connects exchange column, exchange column other end coupled reaction device circulating pump; The shell mid portion is provided with blood pump, and its input connects the blood inlet, and the other end connects the separating plasma pipe; Plasma perfusion pump one end connects threeway; The other end connects active carbon adsorption column, and bioartificial liver's pump one end connects active carbon adsorption column, and the other end connects exchange column; Dialysate pump one end connects exchange column, and the other end connects Dialysis tubing; The bottom is provided with heparin pump in the shell, and separating plasma pipe two ends in addition connects blood pool and threeway respectively, and threeway two ends in addition connects discarded blood plasma jar, plasma perfusion pump respectively, and active carbon adsorption column one end connects the plasma perfusion pump, and the other end connects bioartificial liver's pump; Dialysis tubing one end connects dialysate pump, and the other end connects blood pool, two side openings on the Dialysis tubing; Wherein a side opening connects dialyzate bag; Another side opening connects discarded flow container, and blood pool one end connects plasma bags, separating plasma pipe and Dialysis tubing, and the blood pool other end connects the blood outlet.
2. mixed biology artificial liver vitro supporting device according to claim 1 is characterized in that bioreactor places 37 ℃ and 5%CO 2Constant incubator in.
CN 200810243330 2008-12-26 2008-12-26 Mixed biology artificial liver vitro supporting device Expired - Fee Related CN101455864B (en)

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Application Number Priority Date Filing Date Title
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CN101455864B true CN101455864B (en) 2012-04-18

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108211032B (en) * 2018-02-01 2023-11-17 南方医科大学珠江医院 Combined bioartificial liver support system
CN110448749A (en) * 2019-09-16 2019-11-15 上海市东方医院(同济大学附属东方医院) Cell-circulating bioartificial liver device with oxygen supply
CN111249554B (en) * 2020-03-16 2022-06-14 中南大学湘雅二医院 Biological artificial liver purification circulation unit and artificial liver support system

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