CN103740589A - Human body gastrointestinal tract bionic system and simulation experiment method based on system - Google Patents
Human body gastrointestinal tract bionic system and simulation experiment method based on system Download PDFInfo
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Abstract
The invention relates to a human body gastrointestinal tract bionic system and a simulation experiment method based on the system. The system comprises a system controller, an intestinal flora planting system, a simulation digestion system, a simulation absorption system, a stirring system, a rate control system, a gas path system, a temperature adjusting system, a pH adjusting system, a digestion liquid reagent bottle, an absorbing liquid reagent bottle and a collector. The method comprises the following steps: setting parameters of the control system, preparing planting colloidal particles, planting the intestinal flora, simulating digestion and the like. The system simulates gastrointestinal tract digestion, absorption and intestinal microecology of human bodies under in-vitro conditions, is real in simulation and good in reproducibility, and us applicable to study on the fields of nutriology, toxicology, physiology, microbiology and the like as intelligent control is adopted.
Description
Technical field
The invention belongs to bionics, Human physiology, microbiology, trophology, organic chemistry and analysis and testing technology field.The present invention relates to a kind of human gastrointestinal tract bionic system and the simulation experiment method based on this system, specifically, relate to a kind of isolated condition Imitating food in digestion, absorption and micro ecology of gastrointestinal tract system and the method based on this systems simulation digestion, absorption and microecosystem of human gastrointestinal tract.
Background technology
Human body is a very complicated process to digesting and assimilating of food, is converted to nutrient substance for body growth after food intake.In human body digestive process, two main process almost occur simultaneously: (1) food reduces the size of particle size in digestive tube machinery transport process; (2) macromole in food is hydrolyzed to absorbed into serum after small molecules.Food crushing process mainly occurs in oral cavity and stomach, and the absorption of enzymolysis and nutrient substance and water mainly occurs in small intestine and large intestine.Digestive tract becomes the focus being associated with variety of issue in the investigator's research process of each field (as trophology, toxicology, physiology and microbiology etc.) at present.But unfortunately, the multi stage process of studying the digestion of this complicated human body exists economically and technical difficulty, and also can be subject to the constraint in ethics while relating to potential hazardous and noxious substances in research process.Therefore active demand in-vitro simulated human body a set of flexibly, accurate and can repetitive operation such as digests and assimilates at the model of physiological process.
In past twenties years, various countries scientist is attempting making gi tract model, but most external model is all static, only comprise minority analog parameter, and only for certain organs, as the pipe intestinal digesting system Digestive system of the exploitations in 2002 such as Dutch scientist A.G.Oomen only comprises saliva, gastric juice, pancreatic juice and bile.Yet in physiology, biochemistry and the physicochemical property process of simulation digestive tube complexity, can simulate the material that the food of each meal maybe will study is very important by gastral time, pH and enzymatic hydrolysis condition etc. in digestive process.Therefore, some dynamic many digestion organs models are developed and are applied to research, as American scientist Kong F and Singh PR in people's stomach simulator (HGS) of exploitation in 2010 for simulating food digestion under one's belt.Belgium scientist K.Molly, M.Vande Woestyne, simulation human intestinal microecosystem (SHIME) reactor that W.Verstraete developed and was developed so far in 1993.Although model is complicated, be compared to condition in body, existing gi tract model is still relatively simple, such as they do not comprise Feedback mechanism, the field planting of microorganism, immunity system, and accurate hormone control etc.
For the foundation of human gastrointestinal tract bionic system and the research of method, external starting early, be subject to attention degree also higher, and the research of China relatively lags behind, only have at present mechanism few in number carrying out the research of apparatus and method, as utility model patent grant number CN201634678U discloses a kind of small-sized fermentation device of simulating intestinal environment, this device can be used for that laboratory is aerobic, anaerobism, aerogenesis, the not miniature fermentation such as aerogenesis, can accurately collect and the gas volume that measures fermentation and produce.Invention patent mandate CN102533543B discloses a kind of human intestinal environment of simulating for the device of enteric microorganism cultivation, this device can provide and maintain relative constant temp, humidity, also can have certain vibration, reaches the effect of simulation intestinal environment.Utility model patent grant number CN202658158U discloses a kind of intelligent biology body pipe intestinal digesting systems simulation control device, and this device can be by computer control, Gl tract Digestive tract.Invention patent mandate CN101482460B discloses a kind of unit animal Bionic digestion system and the method based on this systems simulation unit's animal digestion, and this system and method has been realized the process that conditions in vitro Imitating animal gastrointestinal tract is digested and assimilated feed.Invention patent mandate CN101665758B discloses the simulation experiment method that reappears human gastrointestinal tract and microecosystem under a kind of conditions in vitro, the human intestinal microcosm simulation device of the method based on being introduced by Ghent, Belgium university, carries out technological improvement for east crowd's life habit and reaches condition reproduction human gastrointestinal tract system in vitro.
Summary of the invention
For above-mentioned situation, the object of this invention is to provide a kind of human gastrointestinal tract bionic system and the analogue experiment method based on this system, under condition, utilize this system and method can simulate truly human gastrointestinal tract to the digestion of food intake, absorption and intestinal microecology system in vitro.
For achieving the above object, the present invention is achieved through the following technical solutions, and detailed process and step are as follows:
1. the foundation of human gastrointestinal tract bionic system, model comprises Digestive system reagent bottle, absorption liquid reagent bottle, collector, speed control system, air-channel system, humidity control system, pH regulator system, stirring system, intestinal microflora field planting system, simulation Digestive tract, simulation absorption system, central controller.
Wherein, Digestive system reagent bottle is feed liquid reagent bottle 200, pancreatic juice reagent bottle 201, hydrochloric acid reagent bottle 202, sodium bicarbonate reagent bottle 203, sodium hydroxide reagent bottle 204.
Absorption liquid reagent bottle is polyethylene glycol reagents bottle 205.
Collector is liquid waste collector 206, ascending colon dialyzate collector 207, transverse colon dialyzate collector 208, descending colon dialyzate collector 209.
Speed control system is peristaltic pump 1～23 and pump 500, is connected respectively by data line 116 with central controller 900.
Air-channel system is gas reservoir 100 and pipeline 110.
Humidity control system is constant temperature water pot 306, pump 500, pipeline 117, temperature sensor 806 and central controller 900.
PH regulator system is pH meter 800～805, is connected respectively by data line 116 with central controller 900.
Stirring system is magnetic stirring apparatus 400～405, is connected respectively by data line 116 with central controller 900.
Intestinal microflora field planting system comprises Sandwich pot 305, cover and magnetic stirring apparatus, and this interlayer is filled with as internal and external layers of glass material tank; The interface of the shape of falling pagoda is equipped with in the outer nearly top of pot sidewall of Sandwich pot and bottom, between interior outer tank interlayer, is full of thermostat(t)ed water, by silicone tube 117, is connected with constant temperature water pot 306; Sandwich pot seals with synthetic glass, and cover is equipped with pH meter 805, by data line 116, is connected with central controller 900; Gas inlet and outlet, is connected with gas storage tanks 100 by copper pipe 110; Acid solution import connects peristaltic pump 20 and is connected with hydrochloric acid reagent bottle 202 by silicone tube 113; Alkali lye import connects peristaltic pump 21 and is connected with sodium hydroxide reagent bottle 204 by silicone tube 115; Fermented liquid outlet connects peristaltic pump 22 and is connected with ascending colon simulator 302 with small intestine simulator 301 by silicone tube with peristaltic pump 23; Sandwich pot is placed on magnetic stirring apparatus 405, by fermented liquid in rotor stirred pot.
Simulation Digestive tract comprises stomach simulation tank 300, small intestine simulation tank 301, ascending colon simulation tank 302, transverse colon simulation tank 303 and 304 5 laminated glass tanks of descending colon simulation tank, the Link Port of the shape of falling pagoda is equipped with in the outer nearly top of pot sidewall of each laminated glass tank and bottom, connects and pass through silicone tube 117 to be connected with constant temperature water pot 306 between Sandwich pot by silicone tube; Stomach and intestines peristalsis stir simulation by each glass pot with magnetic stirring apparatus 400～404; Sandwich pot seals with synthetic glass, pH meter 800～804 is housed respectively on cover, pH meter is connected with central controller 900 by data line 116, gas inlet and outlet (copper pipe connection), material import and export (connecting by silicone tube through pump 2,4,5,6,7 respectively), acid solution import (being connected with sour reagent bottle 202 by silicone tube 113 through pump 8,10,12,14,16 respectively), alkali lye import are housed respectively on cover, and wherein the perforate of stomach simulation tank cover is connected with feed liquid reagent bottle 200 by silicone tube 111 through peristaltic pump 1; The perforate of small intestine simulation tank cover is connected with pancreatic juice reagent bottle 201 by silicone tube 112 through peristaltic pump 3, and alkali lye import is connected with sodium bicarbonate reagent bottle 203 by silicone tube 114 through peristaltic pump 11; Ascending colon simulation tank, transverse colon simulation tank, the perforate of descending colon simulation tank cover are connected with sodium hydroxide reagent bottle 204 by silicone tube 115 through peristaltic pump 13,15,17 respectively, and cover perforate is connected with polyethylene glycol reagents bottle 205 by silicone tube 116 through peristaltic pump 18,19,20 respectively.
Simulation absorption system, take the ascending colon as example, comprise Sandwich pot 302 and simulation resorber 600, wherein, simulation absorbs dress device 600 fluid inlets and is connected with polyethylene glycol reagents bottle 205 by silicone tube 116 through peristaltic pump 18, and liquid outlet is connected with collector 207 by silicone tube.
During actual design, the quantity of described Digestive system reagent bottle, described absorption liquid reagent bottle, described collector can be for individual arbitrarily.Described simulation Digestive tract, simulation absorption system are two covers totally ten laminated glass tanks.
2. the test method of conditions in vitro Imitating human gastrointestinal tract digestion, absorption and intestinal microecology system made, concrete steps are as follows:
(1) bionic system parameter arranges: human gastrointestinal tract bionic system comprises stomach simulation tank, small intestine simulation tank, ascending colon simulation tank, transverse colon simulation tank and five sandwich glass pots of descending colon simulation tank, between glass pot interlayer, communicate and be connected with 37 ℃ of constant temperature water pots by silicone tube, simulating the temperature in human body alimentary canal, GI wriggling, by put into rotor in simulation tank, drives rotor to stir via magnetic stirring apparatus and is simulated, GI oxygen-free environment is by synthetic glass sealing and fermenting tank mouth, and punching passes into nitrogen, argon gas or carbon dioxide and realizes on the sealing cover of fermentor tank, and ventilation number of times is 2 times/day, 10 minutes/time, according to the pH of human gastrointestinal tract, after the pH of stomach simulation tank measures by pH meter, numerical value feeds back to central controller, central controller remains between 1～2.5 by regulating the addition of hydrochloric acid (0.05M) and sodium bicarbonate (0.5M) to control stomach simulation tank pH, the pH of small intestine simulation tank regulates by hydrochloric acid (0.05M) and sodium bicarbonate (0.5M), pH remains between 6.0～7.5, ascending colon simulation tank, transverse colon simulation tank, the pH of descending colon simulation tank regulates by hydrochloric acid (0.05M) and sodium hydroxide (0.1M), pH remains on respectively 5.5-6.0, 6.0～6.5, between 6.5～7.0, in simulation tank, the volume of liquid is respectively 200ml, 300ml, 500ml, 800ml, 600ml, each is simulated the retention time of liquid in tank and is respectively 2～6h, 3～5h, 12～18h, 24～30h, 14～22h, each peristaltic pump transfer liquid speed and time are respectively feed liquid reagent bottle to stomach simulation tank 20ml/min pump 10min, pancreatic juice reagent bottle is to small intestine simulation tank 9ml/min pump 10min, gastric juice simulation tank is to small intestine simulation tank 21ml/min pump 10min, small intestine simulation tank is to ascending colon simulation tank 28ml/min pump 10min, ascending colon simulation tank is often opened to transverse colon simulation tank 0.6ml/min pump, transverse colon simulation tank is often opened to descending colon simulation tank 0.6ml/min pump, and descending colon simulation tank is often opened to collector 0.9ml/min pump, hydrochloric acid in gastric juice composition is hydrochloric acid and stomach en-, intestinal fluid composition is bile, pancreatin and sodium bicarbonate.
(2) intestinal microflora field planting:
Get nearly healthy male fresh excreta of not accepting antibiotic therapy for 3 months, with 0.1% peptone solution, be diluted to 20% liquid dung suspension, mix, the centrifugal 2min of 500r/min, gets supernatant liquor, and centrifuge tube is preserved.Then by gelling gum 1.875g, xanthan gum 0.1875g, be dissolved in 75mL2g/L citric acid three sodium solution sterilizing.After cooling, be transferred in the aseptic beaker of 500mL, add 1.5mL bacteria suspension, mix.Add 150mL sterilized plant oil, stir 10min, add the sclerosis of 0.1mol/L calcium chloride, underhardening again after deoiling, gauze filters, and micelle can 4 ℃ keeps in Dark Place.
In intestinal microflora field planting tank, add field planting micelle 25g and substratum 500mL, 37 ℃ of waters bath with thermostatic control, magnetic stirrer, anaerobism is cultivated 12h, then change substratum, after cultivating 12h, successfully, the successful bacterium liquid of field planting can pump into small intestine simulation tank and ascending colon simulation tank through peristaltic pump in bacterium field planting again, and the amount of pumping into is respectively 50ml at every turn.
(3) operation of bionic system
A. Bionic digestion step is as follows: a. opens constant temperature water pot, water temperature to 37.5 ℃ in regulating tank, and then ON cycle pump, makes bionic system temperature remain on 37 ℃.B. in intestinal microflora field planting system, magnetic stirring apparatus is opened, after adding substratum in intestinal microflora field planting tank, add previously prepared good field planting micelle, air-channel system intermittently starting in field planting process, every 12h passes into gas in field planting tank, each aeration time is 10min, to bacterium field planting success.C. stomach simulation tank is opened, pH remains between 1.0～2.5, in 24h, add feed liquid 3 times, after feeding in raw material first, every 4h, again add feed liquid, add reduction of feed volume is 200ml at every turn, feed liquid pumps into small intestine simulation tank react 2～6h in stomach simulation tank after, feed liquid all pumps into after small intestine simulation tank, the magnetic stirring apparatus of small intestine simulation tank is opened, pancreatic juice reagent bottle is opened and is pumped into 90ml pancreatic juice to the peristaltic pump of small intestine simulation tank simultaneously, then with sodium bicarbonate, regulate pH to 6.0～7.5, the peristaltic pump that connects small intestine simulation tank and ascending colon simulation tank after 3～5h is opened, feed liquid pumps into ascending colon simulation tank, then colon ascendens magnetic stirring apparatus is opened, the peristaltic pump that now connects intestinal microflora planting device is opened, pump into 50ml field planting bacterium liquid, with HCl (0.05M) and NaOH (0.1M), regulate pH between 5.5～6.0, the volume of feed liquid in ascending colon simulation tank is 500ml, reaction times is 12～18h, then the peristaltic pump that connects ascending colon simulation tank and transverse colon simulation tank is opened, feed liquid pumps into transverse colon simulation tank, the magnetic stirring apparatus of transverse colon simulation tank is opened thereupon, the peristaltic pump that now connects intestinal microflora planting device is opened, pump into 50ml field planting bacterium liquid, with HCl (0.05M) and NaOH (0.1M), regulate pH between 6.0～6.5, the volume of feed liquid in ascending colon simulation tank is 800ml, reaction times is 24～30h, then the peristaltic pump that connects transverse colon simulation tank and descending colon simulation tank is opened, feed liquid pumps into descending colon simulation tank, the magnetic stirring apparatus of descending colon simulation tank is opened thereupon, descending colon simulations tank for HCl (0.05M) and NaOH (0.1M) adjusting pH between 6.5～7.0, the volume of feed liquid in descending colon simulation tank is 600ml, reaction times is 14～22h.
B. bionical absorption step is as follows: first prepare polyglycol solution, it consists of 26.25g/L Macrogol 4000,0.36g/L sodium bicarbonate, and 0.7g/L sodium-chlor, is adjusted to pH9.5 with 1mol/L sodium hydroxide, packs polyglycol solution reagent bottle into.Then the in the situation that of the normal operation of Bionic digestion system, open the peristaltic pump between connection polyglycol solution reagent bottle and ascending colon simulation tank, transverse colon simulation tank, descending colon simulation tank, make polyglycol solution with the flow velocity single flow direction dialyzate collector of 3mL/min.
The present invention has as follows a little:
1. human gastrointestinal tract bionic system of the present invention and the analogue experiment method based on this system have been realized the digestive process of isolated condition Imitating human gastrointestinal tract and the absorption process of colon, total system only need be inputted the operating parameter that each organ is corresponding by alternating interface between man and computer, by computer, digestion, absorption process have automatically been controlled, in experimentation, without there being again manual operation, therefore got rid of the interference of digesting and assimilating extraneous factor in process, simulate true to nature, there is good stability, collimation, and reproducibility.
2. human body gi tract bionic system of the present invention and the analogue experiment method based on this system are applicable to the research in the fields such as trophology, toxicology, physiology and microbiology, as the evaluation to the trophicity of food nourishment composition, probiotics (probiotic bacterium, prebiotics, symphysis unit) etc., validity, security in Nutritional studies; In toxicologic study, external source medicine, microbiotic, poisonous substance etc. are eaten the metabolism research of composition; In Physiologic Studies, by metabolism group, study the impact that intestinal tract flora metabolite produces body; Dynamics research of intestinal microflora etc. in microbiological research.
3. in the present invention, the source of intestinal microflora provides by intestinal microflora field planting system, bacteria flora quantity, kind, ratio and meta-bolites in intestinal microflora simulator are similar to intestinal microflora, can guarantee the stability of flora in enteron aisle simulator, collimation, similarity, and greatly shorten the required time of intestinal microflora field planting.After the field planting of whole system intestinal microflora is stable, applicable to the research of long-term or short-term.
4. the dialysis apparatus that in the present invention, simulation absorbs is placed in digestive organ, can realize the real-time absorption of the small molecule metabolite that metabolism is produced, and avoid the disturbance to enteron aisle Macroflora colonization, simulate true to nature, true absorption closer to enteron aisle to metabolic substd, is more better than the training mode in traditional enteron aisle simulator.
5. in the present invention, meta-bolites can be realized online detection, as aerogenesis after colonic microflora metabolism culture material, produce acid etc., can directly pass through gas phase, liquid phase equipment Inspection.
Accompanying drawing explanation
Fig. 1 human body gi tract of the present invention bionic system model schematic diagram.
Fig. 2 human body gi tract of the present invention bionic system absorption unit schematic diagram.
The implementing procedure figure of Fig. 3 human body gi tract of the present invention bionic system and the analogue experiment method based on this system.
Embodiment
Below in conjunction with specific embodiment, describe the present invention in detail:
The foundation of embodiment 1 human gastrointestinal tract bionic system and digestion, absorption detailed process are as follows:
The foundation of human gastrointestinal tract bionic system: preparation system controller 900 (alternating interface between man and computer, data processor module, device control unit module), data line 116, 118, Digestive system reagent bottle 200～205, liquid-transport pipe-line 111～116, intestinal microflora field planting fermentor tank 305, gi tract simulation tank 300～304, magnetic stirring apparatus 400～405, pH meter 800-805, simulation resorber 600～602, gas-holder 100, gas inlet pipe road 110, peristaltic pump 1～23, constant temperature water pot 306, temperature sensor 806, water pump 500, water pipe 117, liquid header 206～209.
Digestive system reagent bottle 200～205 is connected to peristaltic pump 1～23 by silicone tube and is connected to intestinal microflora field planting fermentor tank 305 and gi tract simulation tank 300～304, by copper gas inlet pipe road 110, connect gas-holder 100 and intestinal microflora field planting fermentor tank 305 and gi tract simulation tank 300～304 again, intestinal microflora field planting tank 305 and gi tract simulation tank 300～304 are placed on magnetic stirring apparatus 400～405, magnetic stirring apparatus 400～405 is connected with central controller 900 by data line 116, by silicone tube 117, be connected in series constant temperature water pot 306, water pump 500, intestinal microflora field planting tank 305 and gi tract simulation tank 300～304, temperature sensor 806 in constant temperature water pot is connected with central controller 900 by data line 118.In real system, above-mentioned gi tract bionic system has a set of parallel system at least, more than also can be two covers, is jointly connected in central controller 900, parallel system desired parameters is identical with above-mentioned single cover bionic system, and the start and stop of system are also synchronized with above-mentioned single cover bionic system.
When experiment starts, open system controller, input intestinal microflora field planting system, and the parameter of gi tract simulator, being respectively 37 ℃ of system temperatures, system venting number of times is 2 times/day, 10 minutes/time, the pH of stomach simulation tank remains between 2.0～2.3 by the interpolation of hydrochloric acid (0.05M) and sodium bicarbonate (0.5M), the pH of small intestine simulation tank remains between 6.0～6.3 by hydrochloric acid (0.05M) and sodium bicarbonate (0.5M), ascending colon simulation tank, transverse colon simulation tank, the pH of descending colon simulation tank remains on respectively 5.5-6.0 by hydrochloric acid (0.05M) and sodium hydroxide (0.1M), 6.0～6.3, between 6.3～6.5, in simulation tank, the volume of liquid is respectively 200ml, 300ml, 500ml, 800ml, 600ml, each is simulated the retention time of liquid in tank and is respectively 4h, 4h, 18h, 30h, 22h, each peristaltic pump transfer liquid speed and time are respectively feed liquid reagent bottle to stomach simulation tank 20ml/min pump 10min, pancreatic juice reagent bottle is to small intestine simulation tank 9ml/min pump 10min, gastric juice simulation tank is to small intestine simulation tank 21ml/min pump 10min, small intestine simulation tank is to ascending colon simulation tank 28ml/min pump 10min, ascending colon simulation tank is often opened to transverse colon simulation tank 0.6ml/min pump, and transverse colon simulation tank is often opened to descending colon simulation tank 0.6ml/min pump.
Then open constant temperature water pot, water temperature to 37.5 ℃ in regulating tank, ON cycle pump, makes bionic system temperature remain on 37 ℃.In intestinal microflora field planting tank, add the previously prepared good field planting micelle of 500ml substratum and 25g, open magnetic stirring apparatus in intestinal microflora field planting system, air-channel system intermittently starting in field planting process, every 12h passes into gas in field planting tank, each aeration time is 10min, in intestinal microflora field planting process, every 12h, change substratum, 24～36h flora field planting success.The successful bacterium liquid of field planting can pump into small intestine simulation tank and ascending colon simulation tank through peristaltic pump, and the amount of pumping into is respectively 50ml at every turn.
Digestive tract starts, first stomach simulation tank is opened, pH remains between 2.0～2.3, in 24h, add feed liquid 3 times, after feeding in raw material first, every 4h, again add feed liquid, add reduction of feed volume is 200ml at every turn, feed liquid pumps into small intestine simulation tank react 4h in stomach simulation tank after, feed liquid all pumps into after small intestine simulation tank, the magnetic stirring apparatus of small intestine simulation tank is opened, pancreatic juice reagent bottle is opened and is pumped into 90ml pancreatic juice to the peristaltic pump of small intestine simulation tank simultaneously, then with sodium bicarbonate, regulate pH to 6.0～6.3, the peristaltic pump that connects small intestine simulation tank and ascending colon simulation tank after 4h is opened, feed liquid pumps into ascending colon simulation tank, then colon ascendens magnetic stirring apparatus is opened, the peristaltic pump that now connects intestinal microflora planting device is opened, pump into 50ml field planting bacterium liquid, with HCl (0.05M) and NaOH (0.1M), regulate pH between 5.5～6.0, the volume of feed liquid in ascending colon simulation tank is 500ml, reaction times is 18h, then the peristaltic pump that connects ascending colon simulation tank and transverse colon simulation tank is opened, feed liquid pumps into transverse colon simulation tank, the magnetic stirring apparatus of transverse colon simulation tank is opened thereupon, the peristaltic pump that now connects intestinal microflora planting device is opened, pump into 50ml field planting bacterium liquid, with HCl (0.05M) and NaOH (0.1M), regulate pH between 6.0～6.3, the volume of feed liquid in ascending colon simulation tank is 800ml, reaction times is 30h, then the peristaltic pump that connects transverse colon simulation tank and descending colon simulation tank is opened, feed liquid pumps into descending colon simulation tank, the magnetic stirring apparatus of descending colon simulation tank is opened thereupon, descending colon simulations tank for HCl (0.05M) and NaOH (0.1M) adjusting pH between 6.3～6.5, the volume of feed liquid in descending colon simulation tank is 600ml, reaction times is 22h.The descending colon of take simulations pot liquid volume reaches after 600ml as system reaches balance.Simulation digestive process starts.
In simulation digestive process, in polyethylene glycol reagents bottle, add polyglycol solution, it consists of 26.25g/L Macrogol 4000,0.36g/L sodium bicarbonate, 0.7g/L sodium-chlor, is adjusted to pH9.5 with 1mol/L sodium hydroxide.Open the peristaltic pump being connected with polyethylene glycol reagents bottle, flow velocity is 3mL/min, and polyoxyethylene glycol pumps into simulation absorption system, and dialyzate flows into receiving flask with polyoxyethylene glycol through silicone tube.
More than show and described ultimate principle of the present invention, principal character and advantage of the present invention.The technician of the industry should understand; the present invention is not restricted to the described embodiments; the knowledge of describing in above-described embodiment and specification sheets illustrates principle of the present invention; the present invention also has various changes and modifications without departing from the spirit and scope of the present invention, and these changes and improvements all fall in the claimed scope of the invention.The claimed scope of the present invention is defined by appending claims and equivalent thereof.
Claims (10)
1. a human gastrointestinal tract bionic system, it is characterized in that: bionic system comprises Digestive system reagent bottle, absorption liquid reagent bottle, collector, speed control system, air-channel system, humidity control system, pH regulator system, stirring system, intestinal microflora field planting system, simulation Digestive tract, simulation absorption system, central controller, wherein:
Intestinal microflora field planting system comprises Sandwich pot, cover and magnetic stirring apparatus, and the interface of the shape of falling pagoda is equipped with in the outer nearly top of pot sidewall of this Sandwich pot and bottom, between interior outer tank interlayer, is full of thermostat(t)ed water, by silicone tube, is connected with constant temperature water pot; Sandwich pot seals with synthetic glass, and cover is equipped with pH meter, by data line, is connected with central controller; Gas inlet and outlet, is connected with gas storage tanks by copper pipe; Acid solution import connects peristaltic pump and is connected with hydrochloric acid reagent bottle by silicone tube; Alkali lye import connects peristaltic pump and is connected with sodium hydroxide reagent bottle by silicone tube; Fermented liquid outlet connects peristaltic pump and is connected with ascending colon simulator with small intestine simulator by silicone tube; Sandwich pot is placed on magnetic stirring apparatus, by fermented liquid in rotor stirred pot.
Simulation Digestive tract comprises stomach simulation tank, small intestine simulation tank, ascending colon simulation tank, transverse colon simulation tank and five Sandwich pots of descending colon simulation tank, the Link Port of the shape of falling pagoda is equipped with in the outer nearly top of pot sidewall of each Sandwich pot and bottom, between Sandwich pot, by silicone tube, connect and be connected with constant temperature water pot by silicone tube, stomach and intestines peristalsis are simulated by magnetic stirrer by each glass pot, Sandwich pot seals with synthetic glass, pH meter is housed respectively on cover, pH meter is connected with central controller by data line, gas inlet and outlet is housed respectively on cover, material import and export, acid solution import, alkali lye import, wherein the perforate of stomach simulation tank cover is connected with feed liquid reagent bottle by silicone tube through peristaltic pump, the perforate of small intestine simulation tank cover is connected with pancreatic juice reagent bottle by silicone tube through peristaltic pump, alkali lye import is connected with sodium bicarbonate reagent bottle by silicone tube through peristaltic pump, ascending colon simulation tank, transverse colon simulation tank, the perforate of descending colon simulation tank cover is connected with sodium hydroxide reagent bottle by silicone tube through peristaltic pump respectively, cover perforate is connected with polyethylene glycol reagents bottle by silicone tube through peristaltic pump respectively.
Simulation absorption system is Sandwich pot and simulation resorber, and simulation resorber fluid inlet is connected with polyethylene glycol reagents bottle by silicone tube through peristaltic pump, and liquid outlet is connected with collector by silicone tube.
Digestive system reagent bottle is feed liquid reagent bottle, pancreatic juice reagent bottle, hydrochloric acid reagent bottle, sodium bicarbonate reagent bottle, sodium hydroxide reagent bottle.
Absorption liquid reagent bottle is in-built polyglycol solution reagent bottle.
Collector is liquid waste collector, ascending colon dialyzate collector, transverse colon dialyzate collector, descending colon dialyzate collector.
Speed control system is peristaltic pump, is connected respectively by data line with central controller.
Air-channel system is gas reservoir and pipeline.
Humidity control system is constant temperature water pot, peristaltic pump, pipeline, temperature sensor and central controller.
PH regulator system is pH meter, is connected respectively by data line with central controller.
Stirring system is magnetic stirring apparatus, is connected respectively by data line with central controller.
Central controller comprises alternating interface between man and computer and central processing unit, by data line, is connected with magnetic stirring apparatus, temperature sensor, pH meter, peristaltic pump.
2. human gastrointestinal tract bionic system according to claim 1, is characterized in that: described Sandwich pot is glass pot Sandwich pot, polytetrafluoroethyltank tank, the outer polytetrafluoroethyltank tank of inner layer glass, internal layer tetrafluoroethylene glass outer tank.
3. human gastrointestinal tract bionic system according to claim 1, is characterized in that: the input of liquid between container, output adopt peristaltic pump, and the action of peristaltic pump is controlled by central processing unit.
4. human gastrointestinal tract bionic system according to claim 1, is characterized in that: gi tract simulation tank is placed on magnetic stirring apparatus, by rotor, stirs pot liquid, and the action of magnetic stirring apparatus is controlled by central processing unit.
5. human gastrointestinal tract bionic system according to claim 1, is characterized in that: on gi tract simulation tank, pH meter is housed, and pressure transmitter, liquidometer, temperature sensor, is all connected with central processing unit.
6. human gastrointestinal tract bionic system according to claim 1, is characterized in that: absorption unit dialysis membrane used is cellulose membrane, the fine film of polypropylene, polymethyl methacrylate film, ethylene vinyl alcohol copolymer membrane, polysulfone membrane, polyamide membrane, polyester aggregation alloy film.
7. the method that human gastrointestinal tract bionic system Gl tract is digested and assimilated according to claim 1, is characterized in that: this method comprises the setting of Controlling System parameter, intestinal microflora field planting, simulation digestion, simulation absorption step, wherein:
Controlling System parameter arranges specific as follows: 37 ℃ of system temperatures, and system venting number of times is 2 times/day, 10 minutes/time, the pH of stomach simulation tank remains between 1.0～2.5 by the interpolation of hydrochloric acid (0.05M) and sodium bicarbonate (0.5M), the pH of small intestine simulation tank remains between 6.0～7.5 by hydrochloric acid (0.05M) and sodium bicarbonate (0.5M), ascending colon simulation tank, transverse colon simulation tank, the pH of descending colon simulation tank remains on respectively 5.5-6.0 by hydrochloric acid (0.05M) and sodium hydroxide (0.1M), 6.0～6.5, between 6.5～7.0, in simulation tank, the volume of liquid is respectively 200ml, 300ml, 500ml, 800ml, 600ml, each is simulated the retention time of liquid in tank and is respectively 2～6h, 3～5h, 12～18h, 24～30h, 14～22h, each peristaltic pump transfer liquid speed and time are respectively feed liquid reagent bottle to stomach simulation tank 20ml/min pump 10min, pancreatic juice reagent bottle is to small intestine simulation tank 9ml/min pump 10min, gastric juice simulation tank is to small intestine simulation tank 21ml/min pump 10min, small intestine simulation tank is to ascending colon simulation tank 28ml/min pump 10min, ascending colon simulation tank is often opened to transverse colon simulation tank 0.6ml/min pump, and transverse colon simulation tank is often opened to descending colon simulation tank 0.6ml/min pump.
Intestinal microflora field planting step is as follows: open constant temperature water pot, and water temperature to 37.5 ℃ in regulating tank, ON cycle pump, makes bionic system temperature remain on 37 ℃.The field planting micelle 25g that adds 500ml substratum in intestinal microflora field planting tank and prepare, open magnetic stirring apparatus in intestinal microflora field planting system, air-channel system intermittently starting in field planting process, every 12h passes into gas in field planting tank, each aeration time is 10min, in intestinal microflora field planting process, every 12h, change substratum, 24～36h flora field planting success.The successful bacterium liquid of field planting can pump into small intestine simulation tank and ascending colon simulation tank through peristaltic pump, and the amount of pumping into is respectively 50ml at every turn.
Simulation digestion step is as follows: stomach simulation tank is opened, pH remains between 1.0～2.5, in 24h, add feed liquid 3 times, after feeding in raw material first, every 4h, again add feed liquid, add reduction of feed volume is 200ml at every turn, feed liquid pumps into small intestine simulation tank react 2～6h in stomach simulation tank after, feed liquid all pumps into after small intestine simulation tank, the magnetic stirring apparatus of small intestine simulation tank is opened, pancreatic juice reagent bottle is opened and is pumped into 90ml pancreatic juice to the peristaltic pump of small intestine simulation tank simultaneously, then with sodium bicarbonate, regulate pH to 6.0～7.5, the peristaltic pump that connects small intestine simulation tank and ascending colon simulation tank after 3～5h is opened, feed liquid pumps into ascending colon simulation tank, then colon ascendens magnetic stirring apparatus is opened, the peristaltic pump that now connects intestinal microflora planting device is opened, pump into 50ml field planting bacterium liquid, with HCl (0.05M) and NaOH (0.1M), regulate pH between 5.5～6.0, the volume of feed liquid in ascending colon simulation tank is 500ml, reaction times is 12～18h, then the peristaltic pump that connects ascending colon simulation tank and transverse colon simulation tank is opened, feed liquid pumps into transverse colon simulation tank, the magnetic stirring apparatus of transverse colon simulation tank is opened thereupon, the peristaltic pump that now connects intestinal microflora planting device is opened, pump into 50ml field planting bacterium liquid, with HCl (0.05M) and NaOH (0.1M), regulate pH between 6.0～6.5, the volume of feed liquid in ascending colon simulation tank is 800ml, reaction times is 24～30h, then the peristaltic pump that connects transverse colon simulation tank and descending colon simulation tank is opened, feed liquid pumps into descending colon simulation tank, the magnetic stirring apparatus of descending colon simulation tank is opened thereupon, descending colon simulations tank for HCl (0.05M) and NaOH (0.1M) adjusting pH between 6.5～7.0, the volume of feed liquid in descending colon simulation tank is 600ml, reaction times is 14～22h.The descending colon of take simulations pot liquid volume reaches after 600ml as system reaches balance.Simulation digestive process starts.
Simulation absorption step is as follows: in simulation digestive process, open the peristaltic pump being connected with polyglycol solution reagent bottle, polyglycol solution pumps into simulation absorption system, and dialyzate flows into receiving flask with polyglycol solution through silicone tube.
8. the method that simulation human gastrointestinal tract according to claim 7 is digested and assimilated, is characterized in that: the required micelle preparation process of intestinal microflora field planting is as follows:
Get nearly healthy male fresh excreta of not accepting antibiotic therapy for 3 months, with 0.1% peptone solution, be diluted to 20% liquid dung suspension, mix, the centrifugal 2min of 500r/min, gets supernatant liquor, and centrifuge tube is preserved.Then by gelling gum 1.875g, xanthan gum 0.1875g, be dissolved in 75mL2g/L citric acid three sodium solution sterilizing.After cooling, be transferred in the aseptic beaker of 500mL, add 1.5mL bacteria suspension, mix.Add 150mL sterilized plant oil, stir 10min, add the sclerosis of 0.1mol/L calcium chloride, underhardening again after deoiling, gauze filters, and micelle can 4 ℃ keeps in Dark Place.
9. the method that simulation human gastrointestinal tract according to claim 7 is digested and assimilated, it is characterized in that: stomach simulator and small intestine simulator pH control and adopt hydrochloric acid and sodium bicarbonate, and ascending colon simulator, transverse colon simulator and descending colon simulator pH control employing hydrochloric acid and sodium hydroxide.
10. the method that simulation human gastrointestinal tract according to claim 7 is digested and assimilated, is characterized in that: polyglycol solution is formulated as follows:
1L polyglycol solution comprises 26.25g Macrogol 4000,0.36g sodium bicarbonate, and 0.7g sodium-chlor, is adjusted to pH9.5 with 1mol/L sodium hydroxide, and polyglycol solution flow velocity is 3mL/min.
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| CN104034912A (en) * | 2014-06-26 | 2014-09-10 | 湖南中本智能科技发展有限公司 | Fully automatic monogastric-animal bionic digestion apparatus |
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