KR101931854B1 - peritoneal circulation apparatus and bioartificial liver support system using the same - Google Patents

peritoneal circulation apparatus and bioartificial liver support system using the same Download PDF

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KR101931854B1
KR101931854B1 KR1020160026939A KR20160026939A KR101931854B1 KR 101931854 B1 KR101931854 B1 KR 101931854B1 KR 1020160026939 A KR1020160026939 A KR 1020160026939A KR 20160026939 A KR20160026939 A KR 20160026939A KR 101931854 B1 KR101931854 B1 KR 101931854B1
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peritoneal
peritoneal fluid
discharge
tube
patient
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KR20170027259A (en
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이석구
이두훈
이지현
이상훈
노정권
장인근
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라이프리버 주식회사
사회복지법인 삼성생명공익재단
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    • A—HUMAN NECESSITIES
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Abstract

The present invention relates to a catheter having a first tube connected to a storage vessel containing a peritoneal fluid and a second tube connected to an infusion catheter for injecting the peritoneal fluid into the abdominal cavity of the patient; A second tube connected to a discharge catheter through which the peritoneal fluid of the patient is discharged, and the other end is connected to the storage vessel; Wherein the second tube comprises a discharge chamber connected to the discharge catheter, a discharge pump connected to the discharge chamber for transferring the peritoneal fluid discharged to the storage container, and a discharge pump connected to the upper end of the discharge chamber, And a pressure indicating pipe capable of detecting the discharged state and the internal pressure of the abdominal cavity.

Description

[0001] The present invention relates to a peritoneal circulation apparatus and a bioartificial liver system using the same,

The present invention relates to a peritoneal circulation device and a bioartificial liver system using the same. More particularly, the present invention relates to a peritoneal circulation device capable of infusion-discharge and continuous circulation, and a peritoneal circulation-type bioartificial system capable of connecting the peritoneal circulation device with a secondary circuit.

Liver, one of the human living organs, is a multipurpose organ that performs more than five hundred complex functions necessary for survival, such as plasma protein synthesis, metabolism and support, as well as detoxification and synthesis and secretion of bile salts or bile pigment. Thus, unlike the heart or kidney, it is impossible to replace the liver function with a simple substitute with pump or dialysis membrane.

In the United States alone, there are about 205,000 people with metabolic disorders, liver cirrhosis, and liver cancer, and about 26,000 people die from terminal liver disease. Recently, the development of organ transplant technology has led to a high survival rate for patients who have undergone liver transplantation, but according to data from the United Network for Organ Sharing (UNOS) Scientific Registry, Only 10% of patients are receiving donated liver, and the number of patients who die in the atmosphere is rapidly increasing.

In 1998, only 16 of the 148 liver transplantation patients in Seoul Central Hospital were benefited from liver transplantation, and despite the development of modern medicine, fulminant hepatic failure (FHF) patients , The mortality rate reaches 90%, but there is no proper treatment method.

Therefore, effective and simple application to such patients is possible, and the liver function support device for minimizing the sequelae of hepatic insufficiency including neurological damage while maintaining the patient's life during liver function recovery, liver regeneration, (Artificial liver, artificial liver) has been urgently required to develop.

However, conventional artificial liver treatments such as hemofiltration, hemodialysis, hemoperfusion, or plasma exchange, which focus only on removing or diluting toxic substances, It was difficult to increase the survival rate. Therefore, studies on bioartificial liver using animal hepatocytes, which have various biological functions performed by hepatocytes, have been actively carried out. Such bioartificial liver can be applied not only to the removal of toxic substances but also to the normal Liver and other metabolic materials necessary for the human body to supply and convert the liver to perform the symptoms and improve the survival time is provided to provide an effect.

Generally, the bioartificial liver consists of a system for separating the patient's plasma, treating it with a bioreactor filled with a high concentration of hepatocytes, and returning it to the patient.

There are a total of nine cases that have been developed into a bioinfosional system since the 1990s and have been subjected to clinical trials for patients with acute hepatic failure. All nine cases support liver function in such a way that plasma or blood circulating extracorporeally is repeatedly circulated extracorporeally through a hepatocyte, hepatocellular carcinoma cell or similar hepatocyte-loaded reactor.

Blood / plasma extracorporeal circulation bioinfusion systems currently in clinical use are accompanied by a number of risks due to the nature of blood / plasma extracorporeal circulation. First, the use of anticoagulants to prevent blood / plasma clotting during CPR is essential. The use of anticoagulants in itself increases bleeding in patients, and especially in patients with acute liver failure, changes in the blood coagulation system have already occurred Proper anticoagulation is not easy for patients. Second, blood loss due to blood / plasma extracorporeal circulation and blood pressure lowering due to dilution may impose a burden on the patient's cardiopulmonary function. In addition, there is a third persistent thrombocytopenia and there is a risk of contamination due to air inflow or blood leakage. Therefore, long-term administration for more than 24 hours is accompanied by a great deal of risk. Lowering the risk requires a bio-in-space system for hepatic insufficiency patients.

On the other hand, the peritoneal membrane, in which many capillaries are distributed, is surrounded by the abdominal cavity including the stomach, spleen, liver, and large intestine, and consists of a semipermeable membrane with smooth movement of blood and lymph. In this regard, peritoneal dialysis, which is performed for the treatment of renal failure and the like, is a therapeutic technique of repeatedly percolating urinary urea by 1 to 3 liters of peritoneal dialysate injected into the abdominal cavity to purify by diffusion osmosis. The above-mentioned peritoneal dialysis is superior to the conventional hemodialysis method in terms of the risk of the extracorporeal blood circulation and the long-term operation is possible. (Non-Patent Document 1).

In addition, several studies have been conducted to investigate the possibility of peritoneal circulation therapy for hepatic insufficiency. Among them, Tympa et al. (Non-Patent Document 2) reported that, when 2 liters of albumin solution was injected into the abdominal cavity of 70% hepatectomized pigs, blood flow disturbance of the whole body and brain was mitigated by hepatic failure compared with the control group. In addition, Hamazaki et al. (Non-Patent Document 3) reported that the survival rate was observed when the alginate capsules harvested from the hepatocyte globular bodies were transplanted into the abdominal cavity of mice that had been treated with hepatectomy by hepatectomy. Soto-Gutierrez et al. Literature 4) reported that the activity of mixed cultured hepatocyte tissues transplanted into the peritoneal cavity of mice with 50% hepatic resection was maintained for one week. These studies show that it is possible to support liver function through the peritoneum.

As a conventional technique for hepatic insufficiency through the peritoneum, Sequana Medical AG has applied for a patent for an artificial liver system in which a dialysis liquid is injected into the peritoneum of hepatic insufficiency patients and the dialysis liquid is discharged through the urethra (Patent Document 1). It is a Fill-Drain system that does not involve dialysis fluid circulating outside the body but does not include a hepatocyte reactor.

Renal Solution has patented a peritoneal circulation bioinfusion system that circulates peritoneal fluid injected into the peritoneal cavity of patients with liver failure via the hepatocyte reactor in vitro (Patent Document 2). In the above-mentioned invention of Renal solution, the adsorption, dialysis, or hepatocyte reactor module is placed in a single peritoneal circulation circuit. Unlike the adsorption and dialysis module in the hepatocyte reactor, cell necrosis occurs within a short time without continuous oxygen supply Therefore, it can be regarded as an impossible structure in the case of a hepatocyte reactor. In addition, for effective hepatic function support through peritoneal circulation, short-term fill-drain or maximum flow of material through continuous flow circulation should occur. Conventional automated peritoneal dialysis devices operate in a Fill-Drain manner, and continuous flow circulation is not possible.

Therefore, there is a need for a peritoneal circulation device capable of achieving a stable continuous flow and an infusion-discharge type peritoneal circulation in a patient, and a bioartificial system capable of applying such a peritoneal circulation device is needed.

1. United States Application 14 / 077,005 2. PCT Application PCT / US1997 / 019489

1. Journal of Korean Medicine Association 2013, 56 (7): 562-568) 2. Tympa. et al., Journal of Investigative Surgery 2011, 24: 129-1331 3. Hamazaki. et al., Hepatogastroenterology 2002, 49 (48): 1514-6 4. Soto-Gutierrez. Et al., Cell Transplant. 2010, 19 (6): 815-22

The present invention provides a peritoneal circulation device capable of realizing a stable continuous flow and an infusion-discharge type peritoneal circulation while applying a gravity discharge method.

Also, the present invention provides a bioartificial system which assists liver function of hepatopulmonary patients by constructing a circulation circuit connected to the peritoneal circulation device and sharing the storage container.

The present invention relates to a catheter having a first tube connected to a storage vessel containing a peritoneal fluid and a second tube connected to an infusion catheter for injecting the peritoneal fluid into the abdominal cavity of the patient; A second tube connected to a discharge catheter through which the peritoneal fluid of the patient is discharged, and the other end is connected to the storage vessel; Wherein the second tube comprises a discharge chamber connected to the discharge catheter, a discharge pump connected to the discharge chamber for transferring the peritoneal fluid discharged to the storage container, and a discharge pump connected to the upper end of the discharge chamber, And a pressure indicating pipe capable of detecting the discharge state and the internal pressure of the abdominal cavity.

The present invention also relates to a peritoneal dialyzer; A bioreactor module for removing toxic substances in the peritoneal fluid contained in animal hepatic cells and discharged from the patient; A first circulation pipe connecting the storage container of the peritoneal circulation device and the bioreactor module to deliver the peritoneal fluid discharged from the storage container to the bioreactor module; And a second circulation pipe connecting the bioreactor module and the storage container to deliver the peritoneal fluid discharged from the bioreactor module to the storage container; And a bio-artificial liver system.

The peritoneal dialyzer according to the present invention may include a pressure display tube to detect the peritoneal fluid discharging state and the intraperitoneal pressure in real time by sensing the peritoneal fluid level in the pressure indicating tube.

In addition, by implementing a bioartificial system constituting a circulation circuit connected to the peritoneal circulation device, it is possible to substitute liver function in vitro until the patient is regenerated or liver transplanted into the bioinductive space system.

1 is a block diagram showing a peritoneal dialyzer according to the present invention.
2 is a view showing the level of the peritoneal fluid in a pressure display tube of a peritoneal dialyzer according to the present invention.
3 is a view showing an embodiment of a pressure indicating tube of a peritoneal dialysis device according to the present invention.
4 is a view showing a bioartificial system according to the present invention.
FIG. 5 is a schematic diagram showing an embodiment of a hepatic insufficiency rat applied to a bioin space system according to the present invention. FIG.
FIG. 6 is a graph showing the results of a peritoneal circulation-type bioartificial liver system according to an embodiment of the present invention when hepatic insufficiency rats were treated with the peritoneal circulation-type bioartificial liver system of the present invention, Ammonia concentration.
FIG. 7 is a graph showing the relationship between the concentration of ammonia in the peritoneal circulation and the hepatic cell reactor circulation circuit when hepatic insufficiency rats were treated with the peritoneal circulation bioartificial liver system of the present invention including a reactor filled with hepatocytes according to an embodiment of the present invention It is a graph comparing changes.
FIG. 8 is a graph showing a result of comparing the peritoneal dialysis effect according to the peritoneal fluid circulation method with the mass transfer rate when treated with the peritoneal circulation system bioartificial system according to the present invention.

The present invention relates to a peritoneal circulation device and a bioartificial liver system using the same. More particularly, the present invention relates to a peritoneal circulation device capable of infusion-discharge and continuous circulation, and a peritoneal circulation-type bioartificial system capable of connecting the peritoneal circulation device with a secondary circuit.

Here, the peritoneal circulation device refers to a device that operates in conjunction with the bioartificial liver system, which will be described later, and which permits the intraperitoneal fluids injected into the abdominal cavity to exchange toxic substances in the body of patients with hepatic failure through the peritoneum.

In addition, the bioartificial liver system refers to a liver assist device for various levels of hepatic insufficiency including acute hepatic insufficiency patients who are waiting for liver transplantation, And can be applied to patients with liver failure in various clinical settings.

More specifically, the peritoneal circulation device of the present invention is connected to a storage container containing a peritoneal fluid on one side and a first tube to which an infusion catheter for injecting the peritoneal fluid into the peritoneal cavity of the patient is connected, And a discharge tube connected to a discharge catheter through which the liquid is discharged, and the other end is connected to the storage container.

In particular, the second tube may include a discharge chamber connected to the discharge catheter, a discharge pump connected to the discharge chamber to move the peritoneal fluid discharged to the storage container, and a discharge pump connected to an upper end of the discharge chamber, And a pressure indicating pipe capable of detecting the internal pressure of the abdominal cavity.

The pressure indicating tube of the present invention may include one or more detection sensors capable of detecting the level of the peritoneal fluid in the pressure indicating tube, and may include a ventilation filter whose upper surface is opened to make contact with the atmosphere. Particularly, the ventilation filter may be formed with a gap of 0.1 to 0.45 mu m.

Meanwhile, the pressure indicating pipe is connected to the inside of the pressure indicating pipe by a difference between a speed (V 1 ) at which the peritoneal fluid is discharged to the discharge chamber and a speed (V 2 ) The peritoneal fluid discharged from the discharge chamber may be introduced or discharged.

At this time, the discharge pump can deliver the peritoneal fluid to the storage container at a flow rate of 30 to 300 ml / min.

In a specific embodiment, the discharge chamber has a height difference of 10 to 90 cm from the abdominal cavity of the patient, and the pressure indicating pipe may be connected by 10 to 90 cm higher than the abdominal cavity.

In addition, the first tube may include an infusion pump connected to the storage container for transferring the peritoneal fluid to the patient's abdominal cavity, an air trap connected to the infusion pump to prevent inflow of air into the infusion catheter, And a pressure sensor positioned between the infusion catheter and the air trap for measuring the pressure of the peritoneal fluid delivered to the abdominal cavity.

In addition, the bioartificial system according to the present invention can be applied to the above-described peritoneal circulation device, a bioreactor module including an animal hepatocyte to remove toxic substances in the peritoneal fluid discharged from the patient, a storage container of the peritoneal dialysis device, A first circulation tube connecting the reactor module to the peritoneal fluid discharged from the storage container to the bioreactor module, and a second circulation pipe connecting the bioreactor module and the storage container, And a second circulation pipe for delivering the water to the storage container.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. Prior to this, terms and words used in the present specification and claims should not be construed as limited to ordinary or dictionary terms, and the inventor should appropriately interpret the concepts of the terms appropriately It should be interpreted in accordance with the meaning and concept consistent with the technical idea of the present invention based on the principle that it can be defined.

Therefore, the embodiments described in this specification and the configurations shown in the drawings are merely the most preferred embodiments of the present invention and do not represent all the technical ideas of the present invention. Therefore, It is to be understood that equivalents and modifications are possible.

FIG. 1 is a configuration diagram of a peritoneal dialyzer according to the present invention. FIG. 2 is a view showing a level of a peritoneal fluid in a pressure display tube of a peritoneal dialyzer according to the present invention. FIG. 5 is a schematic diagram showing an embodiment in which hepatic insufficiency rats are applied to a bioinfusion system according to the present invention. FIG. 6 is a schematic view showing a bioinformatic system according to the present invention. According to one embodiment of the present invention, when hepatic failure mice are treated with the peritoneal circulation bioartificial liver system of the present invention including a reactor in which the hepatocytes are not charged according to FIG. 5, the change of ammonia concentration in the peritoneal circulation and hepatocyte reactor circulation circuit FIG. 7 is a graph showing a comparison between the peritoneal circulation bioinfectors of the present invention including the reactor packed with hepatocytes according to the embodiment of the present invention FIG. 8 is a graph comparing the changes in ammonia concentration in the peritoneal circulation and the hepatic cell reactor circulation circuit when hepatic insufficiency rats were treated with hepatic system. FIG. 8 shows the results obtained when the hepatic venous beagle dog was treated with the peritoneal circulation bioartificial liver system of the present invention , And the peritoneal dialysis effect according to the peritoneal fluid circulation method through mass transfer rate.

Hereinafter, the peritoneal circulation device and the bioartificial liver system using the same according to the present invention will be described in detail with reference to FIGS. 1 to 8 and Examples.

In the present invention, the peritoneal circulation device 100 is operated in conjunction with the bioartificial liver system 200, which will be described later, so that the peritoneal fluid injected into the abdominal cavity causes the toxic substances in the hepatic feces to be exchanged through the peritoneum In particular, the peritoneal dialysis device 100 of the present invention can be applied to various severely hepatic insufficiency patients. Meanwhile, the peritoneal dialyzer 100 can also be used as an automatic peritoneal dialysis device used for peritoneal dialysis in a patient suffering from a renal failure. In this case, the peritoneal fluid can be replaced with a peritoneal dialysis fluid.

Also, the bioartificial liver system 200 refers to a liver assist device for various levels of hepatic insufficiency patients including acute hepatic insufficiency patients who are waiting for a liver transplantation, And can be applied to patients with hepatic dysfunction in various clinical settings.

1, the peritoneal dialyzer 100 according to the present invention is connected to a storage container 130 including a peritoneal fluid, and the other end is connected to an infusion catheter (not shown) 111 and a discharge tube 120 for discharging the peritoneal fluid of the patient are connected to the first tube 110 and the second tube 120 is connected to the other side of the storage tube 130 .

The first tube 110 and the second tube 120 may be a tube for connecting the abdominal cavity of the patient to the storage container 130 and injecting and discharging the abdominal cavity fluid. And may be a circulation tube for injecting the stored peritoneal fluid into the peritoneal cavity of the patient and moving the peritoneal fluid discharged from the peritoneal cavity of the patient to the storage container 130.

The second tube 120 according to the present invention includes a discharge chamber 122 connected to the discharge catheter 121 and a discharge port 122 connected to the discharge chamber 122 to discharge the peritoneal fluid discharged to the storage container 130 And a pressure indicating pipe 124 connected to the upper end of the discharge chamber 122.

Here, the pressure indicating pipe 124 is a pipe having both ends opened and a hollow formed therein. The lower end of the pressure indicating pipe 124 is connected to the upper end of the discharge chamber 122 to discharge the peritoneal fluid, And the like.

The infusion catheter 111 and the discharge catheter 121 may be a catheter for injecting and discharging the peritoneal fluid into the abdominal cavity of a patient with hepatic failure. And may be formed as a dual lumen,

In addition, the discharge chamber 122 is located lower than the abdominal cavity of the patient and can be connected to the discharge catheter 121. This is because the peritoneal fluid discharged from the abdominal cavity of the patient is discharged by the gravitational discharge method.

Meanwhile, the discharge pump 123 of the present invention is positioned between the discharge chamber 122 and the storage container 130, and can discharge the discharged peritoneal fluid to the storage container 130. At this time, the pressure indicating pipe 124 is connected to the upper end of the discharge chamber 122 to sense the discharged state of the peritoneal fluid and the internal pressure of the abdominal cavity.

At this time, the discharge chamber 122 is positioned lower than the abdominal cavity of the patient so that there is a height difference of 10 to 90 cm from the abdominal cavity of the patient, and the pressure indicating pipe 124 may be connected by 10 to 90 cm higher than the abdominal cavity have. Meanwhile, the pressure indicating pipe 124 may be formed to have a length of 20 to 180 cm, and may be connected to the discharge chamber 122 to extend in the longitudinal direction, and may be in the form of a tube extended from the lower portion to the upper portion of the abdominal cavity of the patient. have.

Particularly, the discharge chamber 122 and the abdominal cavity of the patient are differentiated by the above-mentioned height to realize the gravity discharging method. The abdominal cavity of the patient is pressurized to a pressure (about 0.09 bar) corresponding to the height of 90 cm And a height of 10 cm (about 0.01 bar) may be the minimum height for gravity discharge.

In addition, the pressure indicating pipe 124 may include a ventilation filter 125 whose upper surface is opened to make contact with the atmosphere, and the ventilation filter 125 may have a pore of 0.1 to 0.45 탆. Meanwhile, the ventilation filter 125 is provided to block the microorganisms contained in the air from entering the pressure indicating pipe 124, and allows only air to flow in and out.

2 is a graph showing a preferable level (h) of peritoneal fluid in the peritoneal fluid in the pressure indicating tube 124 of the peritoneal dialysis device 100 according to the present invention.

2, the preferred level h of the peritoneal fluid in the pressure indicating tube 124 of the peritoneal dialysis device 100 of the present invention may be the height between the abdominal cavity height of the patient and the discharge chamber 122. This, as lower than the discharge pump 123 flow rate of which is conveying peritoneal fluid (V 2) the flow rate that can be discharged from the height difference between the abdominal cavity and the discharge chamber 122 of the patient with a maximum of (V 1. Max) by At this time, the flow velocity V 1 of the peritoneal fluid discharged from the abdominal cavity becomes equal to the flow velocity V 2 delivered by the discharge pump 123.

That is, the flow velocity V 1 of the peritoneal fluid discharged to the discharge catheter 121 is determined by the peritoneal fluid flow velocity V 2 delivered by the discharge pump 123.

The flow velocity (V 1 .max ) at which the peritoneal fluid discharged from the patient's abdominal cavity can be maximally discharged can be determined by the shape of the catheter, the inner diameter, the intraperitoneal pressure, the height difference between the patient's abdominal cavity and the discharge chamber 122 have. In this case, the peritoneal fluid flow velocity V 1 may be a flow rate of 30 to 300 ml / min.

3 is a view showing an embodiment of the pressure indicating pipe 124 of the peritoneal dialyzer 100 according to the present invention. Referring to Fig. 3 (a), when the discharge pump 123 is stopped or the intraperitoneal pressure is remarkably (V 1.max ) is significantly higher than the peritoneal fluid velocity (V 2 ), the peritoneal fluid level (h) may be at or above the patient's abdominal cavity height. In this case, the intraperitoneal pressure can be confirmed through the water level of the pressure indicating pipe 124.

3 (b), the flow rate V 1 of the peritoneal fluid discharged to the discharge catheter 121 is adjusted to the flow velocity of the peritoneal fluid to be delivered to the storage container 130 by the discharge pump 123 V 2 ), the level h of the peritoneal fluid in the pressure indicating pipe 124 is lowered and eventually the air is introduced into the pressure indicating pipe 124, and the introduced air flows into the storage container 130 Lt; / RTI >

The vented pressure indicating tube 124 provides an air inlet passage to the evacuation chamber 122 when the peritoneal fluid does not flow from the evacuation catheter 121 so that a strong negative pressure It is possible to operate up to the discharge catheter 121 to prevent the risk of the patient.

Meanwhile, the detection sensor included in the pressure indicating pipe 124 can continuously detect the level of the peritoneal fluid in the pressure indicating pipe 124. For example, the upper sensor (not shown) And may include a sensor (not shown).

The upper sensor is a sensor for detecting the change of the inside of the pressure indicating pipe 124 from air to liquid. The upper sensor is a sensor for detecting the change of the intraperitoneal fluid flow velocity V 1 discharged through the discharge catheter 121 from the peritoneal fluid It can be sensed when the flow rate V 2 is significantly higher or when the discharge pump 123 is stopped by an abnormal operation. In particular, the height of the peritoneal fluid of the pressure indicating pipe 124 in the state where the discharge pump 123 is stopped may be set at a height corresponding to a pressure which should preferably not be exceeded because it reflects the intraperitoneal pressure. As an example, the height corresponding to the pressure which should preferably not be exceeded may be a height of 10 to 90 cm from the abdominal cavity.

The lower sensor is used when the flow rate V 1 of the peritoneal fluid discharged to the discharge catheter 121 is significantly lower than the flow velocity V 2 of the peritoneal fluid delivered to the storage container 130 by the discharge pump 123, When the first pipe 110 or the second pipe 120 is blocked, the level of the peritoneal fluid in the pressure indicating pipe 124 is lowered, so that the pressure indicating pipe 124 can be detected to be changed from liquid to gas, At this time, the peritoneal fluid discharging flow rate can be detected to be lowered or stopped.

An air trap 113 may be installed in the first tube 110 of the present invention to prevent inflow of air into the patient's abdominal cavity 11 and may include a pressure sensor 114 to prevent a pressure rise in the abdominal cavity . As a specific aspect, the peritoneal fluid warming device 213 may be additionally provided because there may be a body temperature drop in the patient due to continuous peritoneal circulation.

Referring to FIG. 4, the present invention relates to a bioartificial liver system 200 using a peritoneal circulation apparatus 100.

As described above, the bioartificial system 200 of the present invention refers to a liver assist device for various levels of hepatic insufficiency patients including acute hepatic failure patients waiting for a liver transplantation.

This can replace hepatic function in vitro until the patient is liver regenerated or receives liver transplantation and can be applied to patients with liver failure in a variety of clinical settings.

Particularly, the bioartificial system 200 of the present invention includes a bio reactor module 212 including a hepatocyte, constituting a separate circulation circuit connected while sharing the storage container 130 of (100) It can assist liver function in patients with hepatic insufficiency.

More specifically, the peritoneal dialyzer 100 includes a bioreactor module 212 including an animal hepatocyte, which removes toxic substances in the peritoneal fluid discharged from the patient and assists liver function, the peritoneal dialyzer 100, A first circulation pipe 210 connecting the storage container 130 of the storage container 130 and the bioreactor module 212 to deliver the peritoneal fluid discharged from the storage container 130 to the bioreactor module 212, And a second circulation pipe 220 connecting the reactor module 212 and the storage container 130 to deliver the peritoneal fluid discharged from the bioreactor module 212 to the storage container 130 . Meanwhile, it may include a circulation pump 211 for circulating the peritoneal fluid.

Particularly, the bioreactor module 212 is a core device of the bioartificial system 200 that cleans blood of patients with hepatic failure and assists metabolic functions, and is a technology already known as a bioreactor, so a detailed description thereof will be omitted do.

In the meantime, the bioreactor module 212 may include an exchange for supplying oxygen to the hepatocytes and adjusting the temperature of the hepatocytes in the circulation circuit. The hepatocyte can be perfused with a nutrient-containing drug to supply nutrients to the hepatocytes.

Hereinafter, in order to facilitate understanding of the present invention, experimental examples will be described in detail. It should be understood, however, that the following examples are illustrative only and are not intended to limit the scope of the present invention. Experimental examples of the present invention are provided to enable those skilled in the art to more fully understand the present invention.

<Experimental Example>

Experimental Example  1. According to the invention Liver failure  Peritoneal circulation using rat Bio-in space  Administration test

In this experiment, the liver function supporting ability of the bioartificial liver system 200 including the peritoneal circulation system was confirmed in a small animal such as a rat.

First, a bioartificial liver system 200 as shown in FIG. 5 was implemented, and hepatic insufficiency was induced by injecting D-galactosamine (Sigma-Aldrich) into the prepared rats one day before peritoneal circulation. On the other hand, peritoneal fluid was prepared based on HBSS (Hank's Balanced Salt Solution).

The peritoneal circuit connected to the abdominal cavity of the rat was made into a peritoneal fluid storage container (130) with a 50 ml tube, and the peritoneal fluid of the rat was injected and discharged every 30 minutes.

Also, the bioartificial liver system 200, which is a separate circulation circuit including the bioreactor module 212 filled with hepatocytes, was maintained in a continuous circulation flow, and as a control group, a hepatocyte- The bioartificial system 200 of the present invention was analyzed for the effect of removing ammonia from the peritoneal fluid.

FIG. 6 is a graph comparing changes in ammonia concentration in the peritoneal circulation and the hepatocyte reactor circulation circuit when liver failure mice were treated with the peritoneal circulation-type bioartificial liver system 200 of the present invention including the hepatocyte-free reactor FIG. 7 is a graph comparing ammonia concentration changes in peritoneal circulation and hepatocyte reactor circulation circuit when liver failure mice were treated with the peritoneal circulation system bioartificial liver system 200 of the present invention including a hepatocyte-loaded reactor.

6 and 7, when the results are compared, when hepatic insufficiency rats were treated with the peritoneal circulation system bioartificial system 200 of the present invention including a reactor filled with hepatocytes, it was found that ammonia was effectively removed I could confirm.

Experimental Example  2. According to the present invention Liver failure Beagle dog  Fill-drain Peritoneal circulation and Continuous flow Peritoneal circulation system comparison

In this experiment, hepatic insufficiency index material was measured by circulating peritoneal fluid filled in hepatic vein globe with peritoneal fluid (FD, Fill-Drain) and continuous flow (CF) method.

On the other hand, hepatocytes were not injected into the bioreactor module 212 to reduce the variables affecting the hepatic insufficiency index. Hepatic insufficiency beagle dogs were anesthetized for peritoneal circulation and 600cc peritoneal fluid based on HBSS was injected into the peritoneal cavity.

After 20 minutes, the peritoneal circulation (FD, Fill-Drain) of the infusion-drain system discharged 300 to 400 cc of the peritoneal fluid into the empty storage container 130 and injected the 400 cc peritoneal fluid in the separate storage container 130 into the peritoneal cavity And repeated every 20 minutes. Repeatedly, the peritoneal fluid was sampled every 30 minutes to analyze urea, ammonia, and GPT.

In addition, in the continuous flow (CF) system, 600cc peritoneal fluid and 400cc peritoneal fluid in the storage container 130 were continuously circulated in a continuous flow of 100 cc / min. In addition, urea, ammonia, and GPT (glutamic pyruvic transaminase) were measured at intervals of 30 minutes as in the above-described peritoneal circulation (FD, Fill-Drain).

FIG. 8 is a graph showing a result of comparing the peritoneal dialysis effect according to the peritoneal fluid circulation method with the mass transfer rate when treated with the peritoneal circulation system bioartificial system 200 of the present invention using hepatic insufficiency beagle dogs.

As a result, ammonia had a fast diffusion rate and did not have a high blood concentration, and GPT (glutamic pyruvic transaminase) was slow to diffuse into the peritoneal fluid and thus was not suitable for comparison of circulation method for both ammonia and GPT. However, (FD) and continuous flow (CF) methods. The results are similar to those of the CF method (Fig. 8).

1: patient 11: abdominal cavity
100: Peritoneal circulation device
110:
111: Injection catheter 112: Infusion pump
113: air trap 114: pressure sensor
120:
121: Discharge catheter 122: Discharge chamber
123: discharge pump 124: pressure indicating pipe
125: Aeration filter
130: storage container
200: Bio artificial liver system
210: first circulation pipe
211: circulation pump 212: bioreactor module
213: Heating device
220: second circulation pipe

Claims (9)

A first tube connected to one side of a storage vessel containing the peritoneal fluid and a second tube connected to an infusion catheter for injecting the peritoneal fluid into the abdominal cavity of the patient; And
A second tube connected to a discharge catheter through which the peritoneal fluid of the patient is discharged, and the other end is connected to the storage vessel; / RTI &gt;
The second tube
A discharge pump connected to the discharge catheter and positioned below the abdominal cavity of the patient, a discharge pump connected to the discharge chamber to move the peritoneal fluid discharged to the storage container, and a discharge pump connected to the upper end of the discharge chamber, And a pressure indicating pipe capable of detecting the discharge state and the internal pressure of the abdominal cavity,
The discharge chamber has a height difference of 10 to 90 cm from the abdominal cavity of the patient, the pressure indicating tube has a length of 20 to 180 cm,
The pressure display tube includes an upper sensor and a lower sensor capable of sensing the level of the abdominal fluid in the pressure display tube, wherein the upper sensor is positioned between the abdominal cavity position of the patient and the upper end of the pressure indicating tube, Position and the lower end of the pressure indicating tube.
delete The method according to claim 1,
The pressure indicating pipe
And a ventilation filter whose upper surface is opened to come into contact with the atmosphere.
The method of claim 3,
The ventilation filter
Wherein a pore of 0.1 to 0.45 占 퐉 is formed.
The method according to claim 1,
The pressure indicating pipe
The amount of the peritoneal fluid discharged from the discharge chamber to the inside of the pressure indicating tube due to the difference between the rate (V 1 ) at which the peritoneal fluid is discharged to the discharge chamber and the rate (V 2 ) Wherein the peritoneal dialysis fluid is introduced or discharged.
The method according to claim 1,
The discharge pump
Wherein the peritoneal fluid is delivered to the storage container at a flow rate of 30 to 300 ml / min.
delete The method according to claim 1,
The first tube
An infusion pump connected to the storage container for transferring the peritoneal fluid into the abdominal cavity of the patient;
An air trap connected to the infusion pump for preventing inflow of air into the infusion catheter; And
And a pressure sensor located between the infusion catheter and the air trap for measuring the pressure of the peritoneal fluid delivered to the abdominal cavity.
The peritoneal dialyzer according to any one of claims 1, 3, 4, 5, 6, and 8;
A bioreactor module for removing toxic substances in the peritoneal fluid contained in animal hepatic cells and discharged from the patient;
A first circulation pipe connecting the storage container of the peritoneal circulation device and the bioreactor module to deliver the peritoneal fluid discharged from the storage container to the bioreactor module; And
A second circulation pipe connecting the bioreactor module and the storage container to deliver the peritoneal fluid discharged from the bioreactor module to the storage container; A bioartificial liver system comprising:
KR1020160026939A 2015-08-27 2016-03-07 peritoneal circulation apparatus and bioartificial liver support system using the same KR101931854B1 (en)

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Citations (1)

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US20110144570A1 (en) * 2002-07-19 2011-06-16 Baxter International Inc. Systems and methods for performing peritoneal dialysis

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US6409699B1 (en) 1996-10-22 2002-06-25 Renal Solutions, Inc. Continuous flow-through peritoneal dialysis (CFPD) method with control of intraperitoneal pressure
US8585635B2 (en) 2012-02-15 2013-11-19 Sequana Medical Ag Systems and methods for treating chronic liver failure based on peritoneal dialysis

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Publication number Priority date Publication date Assignee Title
US20110144570A1 (en) * 2002-07-19 2011-06-16 Baxter International Inc. Systems and methods for performing peritoneal dialysis

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