CN108318625B - A kind of human body intestinal canal model visualization Bionic digestion system - Google Patents

A kind of human body intestinal canal model visualization Bionic digestion system Download PDF

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CN108318625B
CN108318625B CN201810069219.5A CN201810069219A CN108318625B CN 108318625 B CN108318625 B CN 108318625B CN 201810069219 A CN201810069219 A CN 201810069219A CN 108318625 B CN108318625 B CN 108318625B
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bionical
bottle
human body
adapter
intestinal canal
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CN108318625A (en
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詹晓北
李志涛
张文龙
高敏杰
彭星桥
蒋芸
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Wuxi Nanyuan Biotechnology Co.,Ltd.
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Jiangnan University
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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Abstract

The invention discloses a kind of human body intestinal canal model visualization Bionic digestion systems, including reaction system and control system;The reaction system includes bionical gastric system, bionical small Im system, bionical big Im system and filtration system;The control system includes PLC controller, peristaltic pump, circulating water chennel;The water inlet pipe of the bionical gastric system, the bionical small Im system and the bionical big Im system is connected by water pipe with the water outlet of the circulating water chennel, the outlet pipe of the bionical gastric system, the bionical small Im system and the bionical big Im system is connected by water pipe with the water inlet of the circulating water chennel, solenoid valve, the solenoid valve on the PLC controller control water pipe are equipped on water pipe.Bionic digestion system of the invention, visual strong, high degree of automation, apparatus module, the mode for simulating gastrointestinal peristalsis are simple and effective.

Description

A kind of human body intestinal canal model visualization Bionic digestion system
Technical field
The present invention relates to a kind of Bionic digestion systems, and in particular to a kind of human body intestinal canal model visualization Bionic digestion system System.
Background technique
The continuous popularization of the in-vitro simulated device of human gut is Food Science, and the research of human nutriology provides huge Big convenience, is gradually received by academia.In the research process of modern food processing, objective accurately evaluation food is in human body Interior digestion process is most important for the effect for determining food component.The in-vitro simulated device of human gut is used in evaluation Food can play a key effect in the intracorporal digestion process of people.The research and development of the novel in-vitro simulated device of people's alimentary canal, for research People enteric microorganism provides very big convenience.By simulate digestion process in vitro in model of different samples and to enteron aisle it is micro- The influence of biology can provide a large amount of valuable data for the research and development of new type functional food, this is mouse experiment or anthropography Hope person's experiment cannot compare.
The prior art simulates slaking apparatus as stomach usually using triangular flask or beaker.When carrying out simulation digestion experiment, first A certain amount of food is fitted into triangular flask or beaker, simulate the gastric juice or intestinal juice are then added into triangular flask, then, by triangle Bottle or beaker are placed on vibration digestion a period of time on water bath with thermostatic control shaking table, this process is to simulate intestinal digestion process, After band digestion, centrifuged or filtered again has digested out and undigested material.Using triangular flask or beaker as gastrointestinal tract When simulating slaking apparatus, since the digestion product in triangular flask or beaker has inhibiting effect to digestion reaction, lead to this kind of digestion The measurement result inaccuracy of experiment.
Compared with being people's gut simulation slaking apparatus with a triangular flask or beaker, 1993, Belgian Molly et al. Develop the dynamic digestion road simulator an of multi-chamber.At the initial stage of development, which only includes 5 by computer control Reactor is composed in series, and simulates duodenum/jejunum, ileum, caecum/colon ascendens, transverse colon and the colon descendens of people respectively.With Afterwards, De Boever in 2001 et al. increases the reactor of a simulation stomach before duodenum/jejunum reactor, is allowed to Become a complete external digestion road model.
CN104851346A discloses a kind of in-vitro simulated system of modularization animal alimentary canal and its human intestine simulation side Method, including five stomach, small intestine, colon ascendens, transverse colon and colon descendens parts, the core of each part are reactor tank;Reactor tank is deposited Digestive juice and intestines bacterium culture medium are stored up, is the place for simulating food digestion, the growth of intestines bacterium;The water interlayer of each reactor tank is and constant temperature Water-bath, which communicates, realizes 37 DEG C of constant temperature effects;The wriggling of each reactor tank is simulated by magnetic agitation.CN102399692A discloses one Kind Full-automatic in-vitro intestinal flora analog model device, including air-channel system, fermentation system, control system;The fermentation system Medium bottle and bioreactor including having agitating device;The control system includes display screen, central processing unit, pH control Instrument processed, temperature control system, peristaltic pump etc..
Both the above human and animal's gastrointestinal tract simulates slaking apparatus, the side wriggled using stirring as simulated gastrointestinal tract Formula has a disadvantage in that stirring produces movement of the raw food in gastrointestinal tract and differs larger with truth, cannot fine simulation True gastrointestinal tract;One of which simulation slaking apparatus has a disadvantage in that, reaction generates only with a reactor come simulated gastrointestinal tract Intermediary and product accumulation in reactor, to digestive ferment generate inhibition.
Summary of the invention
The present invention is directed to the limitation of existing human gastrointestinal tract's in vitro digestion device, provide it is a kind of visual strong, automatically Change degree is high, apparatus module, simulates the mode simply effective human body intestinal canal model visualization Bionic digestion of gastrointestinal peristalsis System.
A kind of human body intestinal canal model visualization Bionic digestion system of the invention, including reaction system and control system;Institute Stating reaction system includes bionical gastric system, bionical small Im system, bionical big Im system and filtration system;The control system includes PLC controller, peristaltic pump, circulating water chennel;The bionical gastric system, the bionical small Im system and the bionical big Im system Water inlet pipe is connected by water pipe with the water outlet of the circulating water chennel, the bionical gastric system, the bionical small Im system and institute The outlet pipe for stating bionical big Im system is connected by water pipe with the water inlet of the circulating water chennel, and electromagnetism is equipped on water pipe Valve, the PLC controller control the solenoid valve on water pipe.
In one embodiment, human body intestinal canal model visualization Bionic digestion system further includes sample delivery device, institute Stating sample delivery device includes first gas bottle and multiple sample bottles, and the multiple sample bottle passes through peristaltic pump and the bionical stomach System is connected, one of them is communicated an opening of the first gas bottle with multiple sample bottles, another opening passes through electromagnetism Valve is connected with the bionical gastric system.
In one embodiment, the bionical gastric system is reacted by the first adapter, the first cartridge type reactor, ball-type Device, the first sampler, the second cartridge type reactor, the second adapter pass sequentially through flange plate and are formed by connecting, and sample is from described first Adapter input, exports from second adapter, and second adapter passes through peristaltic pump and the bionical small Im system phase Even.
In one embodiment, the bionical small Im system is by third adapter, third cartridge type reactor, the second sampling Device, the 4th cartridge type reactor, the 4th adapter pass sequentially through flange plate and are formed by connecting;The lower end that second sampling bottle is equipped with Opening and syringe pump, the third adapter are connected by peristaltic pump with digestive juice bottle, the digestive juice bottle and second gas bottle It communicates.
In one embodiment, the bionical big Im system is sampled by the 5th adapter, the 5th cartridge type reactor, third Device, the 6th cartridge type reactor, the 6th adapter pass sequentially through flange plate and are formed by connecting;5th adapter passes through a wriggling Pump is connected with the lower ending opening of the second sampling bottle, and the third sampling bottle is equipped with lower ending opening.
In one embodiment, the human body intestinal canal model visualization Bionic digestion system further includes filter device, with 4th adapter of the bionical small Im system is connected.
In one embodiment, the first sampling bottle of the bionical gastric system, the bionical small Im system second take It is all provided with useful two glass tubes on the third sampling bottle of sample bottle and the bionical big Im system, is respectively for insertion into pH electrode probe And microscope probe.
In one embodiment, the PLC controller passes through the start and stop of polygon control survey peristaltic pump, syringe pump, solenoid valve And switch.
In one embodiment, N is housed in first gas bottle and second gas bottle2And CO2Mixed gas.
In one embodiment, the third sampling bottle is equipped with an inoculation mouth, for inscribed to the big Im system Enter enteric microorganism.
A kind of advantage of human body intestinal canal model visualization Bionic digestion system of the present invention is:
1., using the reactor of the bionical gastrointestinal tract of liner, may be implemented compared with existing gastrointestinal tract simulates slaking apparatus Heat preservation to sample.And can extruding by the recirculated water of collet between reactor and bionical gastrointestinal tract to bionical gastrointestinal tract, The reciprocating motion of sample is realized, thus the digestion of simulation food in the case where the wriggling of true stomach;
2. three parts of employing mode gastric system simulation people's stomach of the present invention: body of stomach, antrum and pylorus, it can be with independent control The bionical stomach of latex is squeezed or is not under compression in three reaction flasks, and such mode has in terms of structure and function with true people's stomach There is higher similitude;
3. using fibrous filter membrane filtering reacting liquid, the absorption of small intestine is simulated, small molecule nutriment is made not enter big Im system, More true intestinal environment is provided to cultivate enteric microorganism in the big Im system;
4. modularization, each section is relatively independent, individually can be reacted and be analyzed for certain a part in system, operated Form is more flexible.Reactor can be easily increased or decreased as needed, become the structure and function of digestive system very It is convenient;
5. all realizing automation, according to pre-set program, PLC controls adding for sample, digestive juice and buffer Enter, the wriggling of system components and emptying, keeps operation more convenient.
Detailed description of the invention
Fig. 1 is the structural schematic diagram of the human body intestinal canal model visualization Bionic digestion system of the present embodiment one;
Fig. 2 is the structural schematic diagram of bionical gastric system;
Fig. 3 is the structural schematic diagram of bionical small Im system;
Fig. 4 is the structural schematic diagram of bionical big Im system;
Fig. 5 is in Bionic digestion reactor of the invention, existing bionical reactor and mouse intestinal that reference examples provide Digest comparative result figure.
Specific embodiment
Below in conjunction with the drawings and specific embodiments to a kind of human body intestinal canal model visualization Bionic digestion proposed by the present invention System is described in further detail.According to following explanation and claims, advantages and features of the invention will be become apparent from.It needs Bright, attached drawing is all made of very simplified form and using non-accurate ratio, only conveniently, lucidly to aid in illustrating The purpose of the embodiment of the present invention.
Embodiment one
A kind of human body intestinal canal model visualization Bionic digestion system that the present embodiment one provides is as shown in Figure 1, include reaction System, control system and conveying device, the reaction system include bionical gastric system 1a, bionical small Im system 1b and bionical large intestine System 1c;The control system includes PLC controller 4, peristaltic pump 14, circulating water chennel 3;The conveying device includes first gas Bottle 25 and multiple sample bottles 26.
As shown in Fig. 2, the bionical gastric system 1a is by the first adapter 91, the first cartridge type reactor 81, ball-type reactor 71, the first sampler 61, the second cartridge type reactor 82, the second adapter 92 pass sequentially through flange plate and are formed by connecting, and described first Adapter 91 meets input pipe 5a, and the multiple sample bottle 26 is connected by peristaltic pump 14 with the input pipe 5a, first gas One of them is communicated one opening of body bottle 25 with multiple sample bottles 26, another opening passes through solenoid valve 15 and the input pipe 5a is connected.Second adapter 92 meets efferent duct 6a.As shown in figure 3, the bionical small Im system 1b by third adapter 93, Third cartridge type reactor 83, the second sampler 62, the 4th cartridge type reactor 84, the 4th adapter 94 pass sequentially through flange plate connection It forms;Second sampling bottle 62 be equipped with lower ending opening and syringe pump 22, the third adapter 93 by peristaltic pump 14 with Digestive juice bottle 30 is connected, and the digestive juice bottle 30 is communicated with second gas bottle 27.As shown in figure 4, the bionical big Im system 1c By the 5th adapter 95, the 5th cartridge type reactor 85, third sampler 63, the 6th cartridge type reactor 86, the 6th adapter 96 according to It is secondary to be formed by connecting by flange plate;5th adapter 95 passes through the lower ending opening of a peristaltic pump 14 and the second sampling bottle 62 It is connected, the third sampling bottle 63 is equipped with lower ending opening.
Refering to fig. 1~Fig. 4 please be integrate, the third adapter 93 of the bionical small Im system 1b is connect with input pipe 5b, institute The lower ending opening for stating the second sampler 62 is connect with efferent duct 6b, and the 4th adapter 94 is connect with pipeline 12;Efferent duct 6a It is same pipeline with input pipe 5b, is equipped with a peristaltic pump 14 among the pipeline;Filtration system opening is connect with pipeline 12, described Filtration system includes fibrous filter membrane 21, peristaltic pump 14, solenoid valve 15;The 5th adapter 95 and input pipe 5c of big Im system 1c connects It connects, the lower ending opening of third sampler 63 is connect with efferent duct 6c;Efferent duct 6b and input pipe 5c is same pipeline, the pipeline Centre is equipped with a peristaltic pump 14;Efferent duct 6c is equipped with a peristaltic pump 14, and the other end is equipped with receiving flask 28;Each reactor Equipped with circulation water inlet and circulating water outlet, electromagnetism is equipped on all hoses connecting with circulation water inlet and circulating water outlet Valve 15, all recirculated water are flowed out by circulating water outlet pipe 8, the water outlet of described circulating water outlet pipe 8 one end and circulating water chennel 3 Mouth connection;All recirculated water flows back into recirculated water return pipe 7, time of described 7 one end of recirculated water return pipe and circulating water chennel 3 Mouth of a river connection;The PLC controller 4 controls peristaltic pump all in the human body intestinal canal model visualization Bionic digestion system 14, syringe pump 22, solenoid valve 15.
Specifically, the gas in the first gas bottle 25 and the second gas bottle 27 includes N2 and CO2 mixed gas. The first cartridge type reactor 81, ball-type reactor 71, the second cartridge type reactor 82, third cartridge type reactor 83, the 4th cartridge type Reactor 84, the 5th cartridge type reactor 85 are equipped with circulation water inlet 8 and circulating water outlet 9 on the 6th cartridge type reactor 86, with Solenoid valve 14 is equipped on the circulation water inlet 8 and the hose connecting with the circulating water outlet 9;First sampling bottle 61, second sampling bottle 62 and the third sampling bottle 63 are equipped with pH electrode probe 23 and microscope probe 24, wherein institute It states and is additionally provided with lower ending opening and syringe pump on the second sampling bottle 62, be additionally provided with inoculation mouth 34 and lower end on the third sampling bottle 63 Opening.The lower ending opening of second sampling bottle 62 is connect with efferent duct 6b, the lower ending opening of the third sampling bottle 63 with it is defeated Outlet pipe 6c is connected.
The simulated experiment of human body intestinal canal model visualization Bionic digestion system
A kind of human body intestinal canal model visualization Bionic digestion system of the present embodiment, by digesting foodstuff samples in reactor Experiment, assessment human body gastrointestinal model visualization Bionic digestion system simulation effect.
Referring to Fig. 2, before reaction starts, solenoid valve 15 is opened, N is filled with into system2And CO2Mixed gas makes to drain system Interior remaining gas creates oxygen-free environment;Then, solenoid valve 15 is closed, peristaltic pump 14 is started, from input pipe 5a to described bionical A certain amount of sample, gastric juice and HCl are added in gastric system 1a;In gastric system, sample is in the first cartridge type reactor 81, described By repeatedly extruding between ball-type reactor 71, the second cartridge type reactor 82, sample is grated and is broken down into small molecule Substance;After reacting a period of time, sample is discharged through efferent duct 6a.
Referring to Fig. 3, the sample being discharged from the bionical gastric system 1a enters the bionical small Im system 1b by input pipe 5b; A certain amount of Na is added into the bionical small Im system 1b2HCO3, start syringe pump 22, add into the bionical small Im system 1b Enter a certain amount of pancreatic juice and bile, sample is between the third cartridge type reactor 83 and the 4th cartridge type reactor 84 by anti- Multiple to squeeze, sample is further ground and is decomposed;After reacting a period of time, sample enters filtration system, sample warp through pipeline 12 After filtration system filtering, the small-molecule substances such as monosaccharide therein, amino acid are removed as filter liquor, remaining macromolecular substances It flows back into small Im system with a part of water through piping 12, then is discharged through efferent duct 6b.
Referring to Fig. 4, the sample being discharged from the bionical small Im system 1b enters the bionical big Im system by input pipe 5c 1c;Enteric microorganism is accessed into the bionical big Im system 1c from the inoculation mouth 34 of the third sampling bottle 63;Described imitative In raw big Im system 1c, sample and enteric microorganism the 5th cartridge type reactor 85 and the 6th cartridge type reactor 86 it Between by repeatedly extruding, sample is decomposed and by microbial fermentation;After reacting a period of time, sample is discharged to receipts through efferent duct 6c Collect 28 in bottle.
Sample is in the bionical gastric system 1a, the bionical small Im system 1b, the bionical big Im system 1c reaction process In, from the sample tap sampling on sampling bottle corresponding in respective bionic system, the part that test sample is grated and digests accounts for totality Percentage;The pH value of each measurement point is obtained by pH electrode;The variation and the micro- life of enteron aisle of each measurement point sample are obtained by microscope The upgrowth situation of object.
Reference examples
The digestion of human gastrointestinal tract is a complicated process, and traditional gastrointestinal tract simulation digestion reactor is static digestion Simulation, it cannot simulate the physics and physiology course that food occurs in gastrointestinal tract, for example, the variation of pH, gastrointestinal wall wriggling, The emptying etc. of chyme in stomach.Generally using water bath with thermostatic control shaking table, magnetic stirring apparatus and to move up and down the instruments such as mixer simple Food and simulation gastro-intestinal Fluid are carried out after disposably mixing, 37 DEG C of stirred in water bath 1-2h is placed in and disappears to simulate the gastrointestinal tract of food Change process.
The present invention is the dynamic digestion model closer to true gastrointestinal tract, can be to fluid dynamics, the wriggling in gastrointestinal tract Contraction etc. is reappeared well, comprehensively simulates the physical action and physiological processes in gastrointestinal tract.
Step 1: preparing food suspension
Suitable food powders are weighed, are diluted to suspension with the guar gum solution of 0.2% (w/v).
Food powders formula: corn flour 100g, concentrated whey protein powder 40g, edible salt 1g.
Step 2: sample-adding product
Referring to Fig. 1-4, the hydrochloric acid of a certain amount of 0.1mol/L and a certain amount of by stomach is injected into the bionical gastric system 1a Protease, KCl, NaCl composition simulate the gastric juice simulate gastric digestion environment, injected in bionical small Im system 1b a certain amount of 0.1mol/L NaHCO3The digestive environments in enteron aisle are simulated with a certain amount of pancreatic juice and intestinal juice.
Step 3: the course of work
It is added before foodstuff samples, injects 0.6mL simulate the gastric juice to simulate the residual of gastric juice under fasting state.In order to more The process and oral digestion process of true simulation intake corn flour take batch mode that foodstuff samples are added from simulation oesophagus Into stomach model, sample injection time is continuously 5min.During sample introduction, the input rate of simulate the gastric juice is accurately controlled by syringe pump. After sample introduction, close simulation antrum and pylorus, to simulate digestion process of the food in no gastric emptying.Pass through hydraulic pressure pair simultaneously The pylorus and antrum of stomach model are compressed, and compression frequency is 3 beats/min, suppressed range 2.5mm.Distinguish to foodstuff samples After digesting 1h, gastric digestion object is entered into bionical small Im system 1b by wriggling mode, and take batch mode by foodstuff samples It is added in bionical small Im system 1b model from simulation oesophagus, sample injection time is continuously 10min.During sample introduction, pass through syringe pump The input rate of accurate control simulated intestinal fluid and pancreatic juice after sample introduction, carries out wriggling compression, peristaltic pressure to enteron aisle by hydraulic pressure Contracting frequency is 10 beats/min, suppressed range 1cm.After foodstuff samples digest 3h respectively, the digested object of enteron aisle is all taken Out, its reduced sugar and protein content are surveyed.Of the invention enteron aisle visualization Bionic digestion reactor, existing bionical reactor and The digested Comparative result of mouse intestinal is as shown in Figure 5.
As seen from Figure 5, bionical reactor of the invention is adopted compared with the bionical reactor of tradition, it being capable of more life-like simulation With the processes result of intravital mouse gastric digestion food, the clear superiority of bionical reactor of the invention has been embodied.
Although the present invention has been described by way of example and in terms of the preferred embodiments, it is not intended to limit the invention, any to be familiar with this skill The people of art can do various change and modification, therefore protection model of the invention without departing from the spirit and scope of the present invention Enclosing subject to the definition of the claims.

Claims (9)

1. a kind of human body intestinal canal model visualization Bionic digestion system, which is characterized in that including reaction system and control system;Institute Stating reaction system includes bionical gastric system, bionical small Im system, bionical big Im system and filtration system;The control system includes PLC controller, peristaltic pump, circulating water chennel;The bionical gastric system, the bionical small Im system and the bionical big Im system Water inlet pipe is connected by water pipe with the water outlet of the circulating water chennel, the bionical gastric system, the bionical small Im system and institute The outlet pipe for stating bionical big Im system is connected by water pipe with the water inlet of the circulating water chennel, and electromagnetism is equipped on water pipe Valve, the PLC controller control the solenoid valve on water pipe;The filtration system includes fibrous filter membrane, peristaltic pump, solenoid valve, institute Filtration system is stated to be connected by pipeline with the 4th adapter of bionical small Im system;The bionical gastric system, bionical small Im system And the reactor in bionical big Im system is the reactor of liner gastrointestinal tract, also, the liner gastrointestinal tract is soft.
2. human body intestinal canal model visualization Bionic digestion system according to claim 1, which is characterized in that human body intestinal canal mould It further includes sample delivery device that type, which visualizes Bionic digestion system, and the sample delivery device includes first gas bottle and multiple samples Product bottle, the multiple sample bottle are connected by peristaltic pump with the bionical gastric system, one of the first gas bottle be open and One of them is communicated multiple sample bottles, another opening is connected by solenoid valve with the bionical gastric system.
3. human body intestinal canal model visualization Bionic digestion system according to claim 1, which is characterized in that the bionical stomach System is by the first adapter, the first cartridge type reactor, ball-type reactor, the first sampler, the second cartridge type reactor, the second switching Head passes sequentially through flange plate and is formed by connecting, and sample input from first adapter, from second adapter output, described the Two adapters are connected by peristaltic pump with the bionical small Im system.
4. human body intestinal canal model visualization Bionic digestion system according to claim 1, which is characterized in that described bionical small Im system is successively led to by third adapter, third cartridge type reactor, the second sampler, the 4th cartridge type reactor, the 4th adapter Flange plate is crossed to be formed by connecting;The lower ending opening and syringe pump that second sampling bottle is equipped with, the third adapter pass through compacted Dynamic pump is connected with digestive juice bottle, and the digestive juice bottle is communicated with second gas bottle.
5. human body intestinal canal model visualization Bionic digestion system according to claim 1, which is characterized in that described bionical big Im system is successively led to by the 5th adapter, the 5th cartridge type reactor, third sampler, the 6th cartridge type reactor, the 6th adapter Flange plate is crossed to be formed by connecting;5th adapter is connected by a peristaltic pump with the lower ending opening of the second sampling bottle, described Third sampling bottle is equipped with lower ending opening.
6. human body intestinal canal model visualization Bionic digestion system according to claim 1, which is characterized in that the bionical stomach On the third sampling bottle of first sampling bottle of system, the second sampling bottle of the bionical small Im system and the bionical big Im system Useful two glass tubes are all provided with, pH electrode probe and microscope probe are respectively for insertion into.
7. human body intestinal canal model visualization Bionic digestion system according to claim 1, which is characterized in that the PLC control Device processed passes through polygon control survey peristaltic pump, syringe pump, the start and stop of solenoid valve and switch.
8. human body intestinal canal model visualization Bionic digestion system according to claim 2 or 4, which is characterized in that the first gas N is housed in body bottle and second gas bottle2And CO2Mixed gas.
9. human body intestinal canal model visualization Bionic digestion system according to claim 6, which is characterized in that the third takes Sample bottle is equipped with an inoculation mouth, for being inscribed to the big Im system into enteric microorganism.
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PCT/CN2018/081004 WO2019144496A1 (en) 2018-01-24 2018-03-29 Visual bionic digestive system of human gastrointestinal tract model
US16/121,720 US12118896B2 (en) 2018-01-24 2018-09-05 Visual bionic digestive system for human gastrointestinal tract model

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