AU2018318791B2

AU2018318791B2 - Method for fabricating integrated model of flexible human esophagus, stomach, duodenum, and small intestine, and dynamic in vitro biomimetic digestive system thereof

Info

Publication number: AU2018318791B2
Application number: AU2018318791A
Authority: AU
Inventors: Xiaodong Chen; Zhizhong DONG; Zhenkai LIAO; Minghui Liu; Jinfeng MENG; Yong Wang
Original assignee: Cofco Nutrition and Health Research Institute Co Ltd
Current assignee: Cofco Nutrition and Health Research Institute Co Ltd
Priority date: 2017-08-14
Filing date: 2018-08-11
Publication date: 2021-07-01
Anticipated expiration: 2038-08-11
Also published as: WO2019034008A1; AU2018318791A1

Abstract

Provided are a method for fabricating an integrated model of a flexible human esophagus, stomach, duodenum, and small intestine, and a dynamic in vitro biomimetic digestive system thereof. The method for preparation comprises scanning the internal and external structures of a human esophagus, stomach, duodenum, and small intestine to obtain a corresponding mold; applying a mold release agent evenly on the mold; pouring an elastic liquid material into the mold; waiting for same to cure, then releasing from the mold to separately obtain an esophagus model (a), stomach model (b), duodenum model (c), and small intestine model (d); cleaning the surfaces of same, then air-drying; using an adhesive to bond together, in sequence, the esophagus model (a), stomach model (b), duodenum model (c), and small intestine model (d) to obtain an integrated model; by means of a peristaltic pressing apparatus, applying pressure to the two sides of each of the esophagus model (a), stomach model (b), and duodenum model (c) to achieve biomimetic motion. It is thus possible to simulate the process of digestion of the human stomach and duodenum, providing accurate experimental data for research on the human digestive system while also appropriately reducing experimentation on animals and humans.

Description

Method for Fabricating Integrated Model of Flexible Human Esophagus, Stomach, Duodenum and Small Intestine, and Dynamic in Vitro Biomimetic Digestive System Thereof

FIELD The present disclosure falls within the field of in vitro digestion simulation, in particular to a method for fabricating an integrated model of flexible human esophagus, stomach, duodenum and small intestine, and a dynamic in vitro biomimetic digestive system thereof. The method is used for the device which can simulate the digestion process of human stomach and duodenum and can also be used for the in vitro digestion experiment of food and medicine.

BACKGROUND The in vitro human biomimetic digestive system is a device that simulates human digestive system and digestive process in vitro. From the perspective of engineering, the in vitro biomimetic digestive system can be regarded as a dynamic system composed of one or more flexible biochemical reactors. Among them, it is essential to establish a complete model of in vitro biomimetic human esophagus, stomach, duodenum and small intestine. Thanks to its characteristics of low cost, convenience, high efficiency, no ethical restrictions and ease of local sampling or specific sampling, in vitro biomimetic digestive system has partially replaced clinical trials or animal tests, and has obtained many important research results in the study of bioavailability of food nutrients, drug sustained release, digestive stability of sensitizing ingredients, digestive survival rate of probiotics, and is widely used in food, pharmaceutical, medical, environmental and other research fields. Researchers have made many beneficial explorations on optimizing the in vitro gastric biomimetic system on the road towards more realistic. Among them, it is essential to perform biomimetics on the morphological structure, movement mode and digestion environment of the real digestive system, that is, through these three biomimetic modes, the complex and non-steady gastric digestion system can be disassembled into biochemical reactor systems that can be detected and analyzed; these three biomimetic modes not only directly determine the feeding mode of digestive juice (including digestive enzymes), the mixing mode of reactants (ingredients, etc.) and digestive juice and the discharge mode of reaction products, but also affect the crushing effect and digestion effect of

17678736_1 reactants in the entire digestive tract. Therefore, the optimization of morphological biomimetics, kinematic biomimetics, and biomimetics of the digestive environment is a key research issue for the development of in vitro biomimetic systems. The construction of quasi-real in vitro human esophagus, stomach, duodenum and small intestine is the basic and the most important section in carrying out these tasks. To carry out the biomimetic digestion experiment on human organs, it is usually necessary to make some relevant digestive system models and assign certain actions to the digestive system models, so that they have the digestive function of human organs and are used for the study of human digestive system. At present, the digestive organ model used in the study of the digestive system is quite different from the real human digestive organ in terms of functions, and cannot completely simulate the real digestive system of the human body. Therefore, many unreliable collected test data will be generated in scientific research, which is not conducive to scientific research. Up to now, most of the in vitro digestion and absorption simulating devices developed at home and abroad have not played a biomimetic and real role in the anatomy of human body. The commonly used device is a stirring reactor (glassware), which is used to simulate the digestion reaction system. For example, Chinese patent document CN 103740589 discloses a biomimetic system for human gastrointestinal tract and a simulation experiment method based on this system, which ignores the stirring principle of flexible reactor in the real digestion process and its interaction with food. SUMMARY Therefore, the technical problem solved by the present disclosure lies in making a digestion model with quasi-real physiological structure characteristics and dimensions, which is used in the biomimetic digestion experiment to improve the accuracy of the experiment and realistically simulate the digestion and emptying process of the human stomach and duodenum, so as to provide accurate data for the experiment. Therefore, the present disclosure provides a preparation method for an integrated model of flexible human esophagus, stomach, duodenum and small intestine as well as a dynamic in vitro biomimetic digestive system thereof. On the one hand, the present disclosure provides a method for preparing an integrated model of flexible human esophagus, stomach, duodenum and small intestine, comprising the following steps:

17678736_1 step 1: scanning the internal and external structures of human esophagus, stomach, duodenum and small intestine by using a 3D scanner to prepare esophagus mold, stomach mold, duodenum mold and small intestine mold; step 2: applying a mold release agent evenly on the molds, pouring elastic liquid material on the molds, then releasing the molds after their curing to obtain esophagus model, stomach model, duodenum model and small intestine model, and performing drying after surface cleaning; Step 3: Punching holes in the stomach model, duodenum model and small intestine model, respectively, inserting and fixing a flexible tube in the holes as a secretion tube; Step 4: Adhesive is used to bond biomimetic human esophagus model, stomach model, duodenum model and small intestine model in the order of structures to obtain an integrated model. In the step 1, a three-dimensional scanner is used to scan the internal and external structures of human esophagus, stomach and duodenum, respectively, and the scanned images are modeled and saved into pictures in STL format through three-dimensional modeling software; the three-dimensional images are input into a 3D printer, and the human esophagus mold, stomach mold and duodenum mold are successively prepared. The method for preparing the esophagus model and the duodenum model comprises the following steps: according to the inner and outer diameter dimensions of the human esophagus and duodenum obtained by three-dimensional scanning, the esophagus mold and the duodenum mold with a flat silicone plate structure are respectively made using the silicone material, the lengths of the molds are respectively equal to the length of esophagus and the length of duodenum, and the widths of the molds are equal to the outer diameter perimeter of the esophagus and that of the duodenum; the two silicone plates are coated with the binding agent layer by layer along both sides in their length directions, and the esophagus model and the duodenum model are respectively prepared after curing. The method for preparing the small intestine model comprises the following steps: molding smooth holes with certain interval, diameter and depth on the perspex sheet to prepare the small intestine mold; applying a mold release agent on the perspex sheet mold, pouring an elastic liquid material on the small intestine mold, releasing the mold after curing, and drying the mold after surface cleaning to prepare the preliminary model of small intestine; the preliminary model of small intestine is coated with binding agent layer by layer along both sides in its length

17678736_1 direction, and the small intestine model is prepared after curing. The method for preparing the stomach model comprises the following steps: using a 3D printer to print the internal and external models of the stomach mold according to the internal and external dimensions of human stomach as obtained through three-dimensional scanning; applying a mold release agent to the external surface of the internal model and the internal surface of the external model, respectively; pouring an elastic liquid material into the gap formed by the internal model and the external model, after curing, the left and right stomach models are prepared by demolding, and are dried after surface cleaning; applying a binding agent layer by layer on both sides of the dried stomach model along its length direction; after curing, the stomach model is prepared. Apply silicone binding agent layer by layer on the joints of both sides along the length direction of each model after drying, with the curing duration for each layer of silicone binding agent being 2.5 - 3.5 hours, and apply 5 - 7 layers; seal the outlet at one end of mold and inject water-soluble red liquid fuel from the other end to detect whether there is liquid leakage from the mold. The secretion tube used in the step 3 is a silicone tube with an outer diameter of 2 mm, an inner diameter of 1 mm and a length of 300 - 400 mm. In the step 3, 12 holes are punched on each of two sides of the stomach wall of the stomach model using a puncher with diameter of 5 mm, at least one hole is punched at the position of major papilla of the duodenum model, the secretion tubes are fixed in the corresponding holes one by one, the insertion end port of the secretion tubes does not exceed the inner surface of the stomach model and the duodenum model, and is communicated with the inner surface of the stomach model and the duodenum model. The elastic liquid material used is silicone material with tensile strength of 4-6 kgf/cm2 , elongation at break of 300-800%, tensile strength of 20-30 kgf/cm 2 and linear shrinkage of <

0.5%. On the other hand, the present disclosure also provides a dynamic human stomach-duodenum in vitro biomimetic digestive system, which comprises a heating incubator as well as an esophagus model, a stomach model, a duodenum model, a peristaltic extrusion device and a digestion and emptying unit which are located in the heating incubator, wherein the esophagus model, the stomach model and the duodenum model are connected with each other; the

17678736_1 peristaltic extrusion device is respectively arranged on both sides of the esophagus model, the stomach model and the duodenum model to realize the biomimetic movement of the esophagus model, the stomach model and the duodenum model; the digestion and emptying unit comprises a feeding device connected with the inlet of the esophagus model, a digestive juice adding device connected with the stomach model and the duodenum model and an emptying device connected with the outlet end of the duodenum model; The food enters the esophagus model through the feeding device, and the food sequentially enters the stomach model and the duodenum model under the action of the peristaltic extrusion device. The digestive juice in the digestive juice adding device enters the stomach model and the duodenum model, and is mixed with the food. The food is excreted by the emptying device after the food digestion is completed. The esophagus model, the stomach model, and the duodenum model are silicone models which are detachable and fixedly connected to each other, and designed in a 1:1 ratio to real human esophagus, stomach, and duodenum. The esophagus model, the stomach model and the duodenum model are respectively provided with a temperature measuring element and a pH collecting element. The temperature measuring elements are respectively distributed at the inlet of the esophagus module, the inlet of the stomach model and the inlet of the duodenum model; the pH collecting elements are arranged at the pylorus below the stomach model and the outlet of the duodenum model; the temperature measuring elements and the pH collecting elements are connected with the computer to realize data connection. The stomach model is provided with a plurality of gastric juice inlets on both its front and rear sides, and the front part of the duodenum model is provided with a bile inlet and a pancreatic juice inlet. The digestive juice adding device is respectively connected with the gastric juice inlet, the bile inlet and the pancreatic juice inlet for injecting gastric juice, bile and pancreatic juice into the stomach model and the duodenal model respectively. The peristaltic extrusion device comprises a peristaltic device for driving the esophagus model, the stomach model and the duodenum model to produce biomimetic peristalsis, respectively, comprising multiple sets of esophageal eccentric convex wheels and esophagus fixed concave wheels engaged on both sides of the esophagus model, multiple sets of stomach eccentric concave wheels and stomach eccentric flat wheels on both sides of the stomach model, and

17678736_1 multiple sets of duodenum eccentric concave wheels and duodenum fixed convex wheels on both sides of the duodenum model; the eccentric convex wheels, eccentric concave wheels and eccentric flat wheels rotate by driving a motor, respectively. The peristaltic extrusion device also comprises a stomach extrusion device whose extrusion direction is perpendicular to the peristaltic action force direction of the peristaltic device, wherein the stomach extrusion device is arranged on both sides of the stomach model and comprises an extrusion push rod, an extrusion motherboard and a plurality of groups of extrusion heads; the extrusion push rod is fixedly connected with the extrusion motherboard to drive the extrusion motherboard to make reciprocating movement, and the plurality of groups of extrusion heads are vertically arranged on the extrusion motherboard to form threaded connection with the extrusion motherboard. The pylorus position below the stomach model is also provided with a pylorus clamp having the same action force as the stomach extrusion device. The pylorus clamp comprises a front extrusion plate, a rear extrusion plate and a pylorus push rod. The pylorus push rod is fixedly connected with the front extrusion plate to drive the front extrusion plate to make reciprocating movement. A trapezoidal convex structure is molded on the rear extrusion plate; a trapezoidal concave structure is molded on the front extrusion plate; the front extrusion plate and the rear extrusion plate form complete engagement. The heating incubator comprises an incubator body, a heating lamp arranged inside the incubator body and a temperature control device; the heating lamp is used to provide temperature for the biomimetic organ, and the heating lamp is electrically connected with the temperature control device to control the heating temperature of the heating lamp. The digestive system is also provided with an adjusting device for adjusting the placement angle of the heating incubator, which comprises a driving motor and a connecting device; the connecting device is designed to connect the driving motor to the heating incubator; and the angle of the heating incubator is adjusted through the leftward and rightward rotation of the driving motor. The feeding device comprises a funnel supporting base and a funnel, wherein the funnel supporting base is arranged above the outside of the heating incubator, and the lower end of the funnel is communicated with the inlet of the esophagus model. At least three groups of the digestive juice adding devices are provided, wherein the digestive

17678736_1 juice adding device comprises a juice tank, a digestive juice peristaltic pump and a juice inlet pipe, the juice inlet of the digestive juice peristaltic pump is correspondingly connected with the juice tank, the liquid outlet of the digestive juice peristaltic pump is correspondingly connected with one end of the juice inlet pipe, and the other end of the juice inlet pipe is respectively connected with the corresponding bile inlet, pancreatic juice inlet and multiple gastric juice inlets on the stomach model and the duodenum model. The emptying device comprises an emptying peristaltic pump and an emptying tube connected to the emptying peristaltic pump, wherein the emptying tube is connected to the outlet end of the duodenum model. The technical solution of the present disclosure has the following advantages: A. The present disclosure adopts the method of three-dimensional scanning combined with 3D printing to make flexible human esophagus, stomach and duodenum molds, adopts the mechanical method to prepare the small intestine mold, then uses flexible elastic material to make 1:1 flexible human esophagus, stomach and duodenum molds by turning over, arranges secretion tubes on the stomach, duodenum and small intestine, then connects the flexible human esophagus, stomach duodenum and small intestine in the sequence structure, and makes an integrated model of flexible human esophagus, stomach, duodenum and small intestine. The model has the characteristics and dimension of quasi-real physiological structure, and has a series of advantages such as the secretion function of digestive juice and flexibility. The model can be used in the biomimetic digestion experiment to improve the accuracy of the experiment. B. The present disclosure uses organic silicone rubber (other elastomers can also be used) to make biomimetic human esophagus, stomach, duodenum and small intestine models. The prepared models simulate the real human digestive tract in terms of internal form, external form and dimension. Simulation is the most important part of the form biomimetics, so morphology and structure directly determine the mixing mode and residence time of digest in the digestive system. In addition, the prepared model has the function of adding digestive juice flow, with the acceleration rate and the quantity of flow simulating the real manner of adding human digestive juice flow. At the same time, the organic silicone rubber has good elasticity and can simulate the movement of human digestive system in vitro by applying certain mechanical force. C. The dynamic human stomach-duodenum in vitro biomimetic digestive system provided by the present disclosure comprises a human esophagus model, a stomach model, a duodenum

17678736_1 model, a peristaltic extrusion device, a heating incubator and a digestion and emptying unit, while the consumption emptying unit comprises a feeding device, a digestion liquid adding device and an emptying device arranged at the outlet of the duodenum model; the esophagus model, a stomach model and a duodenum model are used to simulate real human's food digestion process, which is more scientific than the current method of using a beaker to stir, dissolve and flush to study the digestion process of food and drugs, and at the same time can appropriately reduce the animal experiment and human experiment to a certain extent. D. The present disclosure models the real human stomach, esophagus and duodenum according to the size ratio of 1:1 to prepare an esophagus model, a stomach model and a human duodenum model. The sizes, shapes and internal physiological structures of these models are consistent with those of real human stomach and duodenum. These models are soft but have high elasticity and tear resistance. The peristalsis extrusion device can simulate the peristalsis and deformation of human digestive organs. The heating incubator is designed to heat the esophagus, stomach and duodenum. The food and digestive juice are added to the digestive system by adding a digestion and emptying unit. The emptying device is used to assist the discharge of digested food. These models can simulate the digestion process of real human in all directions. The test data is reliable. BRIEF DESCRITION OF THE DRAWINGS In order to illustrate more clearly the detailed description of the present disclosure or the technical solutions in the prior art, the following brief introduction is given to the detailed description or the attached drawings needed in the description of prior art. It is obvious that the attached drawings in the following description are some detailed description of the present disclosure, and those skilled in the art can obtain other attached drawings without making any creative effort. Figure 1 is a schematic diagram of the human esophagus-stomach-duodenum-small intestine silicone model according to the present disclosure; Figure 2 is the structure diagram of small intestine mold; Figure 3 is a schematic diagram of the human esophagus-stomach-duodenum silicone model according to the present disclosure; Figure 4 is a schematic diagram of the peristaltic device, the extrusion device and the heating insulating device according to the present disclosure;

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Figure 5a is the front view of the esophageal eccentric convex wheel as set forth as Figure 4; Figure 5b is the right view of the eccentric convex wheel of the esophagus as set forth as Figure 5a; Figure 6a is the front view of the esophageal fixed concave wheel in Figure 4; Figure 6b is the right view of the esophageal fixed concave wheel as set forth as Figure 6a; Figure 7a is the front view of the eccentric concave wheel of the stomach and duodenum as set forth as Figure 4; Figure 7b is the right view of the gastric and duodenal eccentric concave wheels as set forth as Figure 7a; Figure 8a is the front view of the eccentric flat wheel of stomach as set forth as Figure 4; Figure 8b is the right view of the gastric eccentric flat wheel as set forth as Figure 8a; Figure 9a is the front view of the duodenal fixed convex wheel as set forth as Figure 4; Figure 9b is the right view of the duodenal fixed convex wheel as set forth as Figure 9a Figure 10a is the front structural view of the stomach extrusion device as set forth as Figure 4; Figure 10b is a schematic diagram of the lateral structure of Figure 10a Figure 10c is a schematic diagram of the overlooking structure of Figure 10a; Figure 11 is a schematic of the details of the pyloric clamp as set forth as Figure 4; Figure 12 is a schematic diagram of the digestive system placement angle adjusting device according to the present disclosure; Figure 13 is a schematic diagram of the feeding device, assisted emptying device and digestive juice adding device according to the present disclosure; In the drawings: a-esophagus model; b-stomach model; c-duodenum model; c l-circular folds; d-small intestine model, d1-villi; 1,2,3-temperature measuring elements; 4-gastricjuice inlet; 5-bile inlet; 6-pancreatic juice inlet; 7, 8, 9-pH collecting elements; 10-Heating lamp, 101-Heating lamp for lower layer of incubator, 102-Heating lamp for lower layer of incubator; 11-Incubator body; 12-Heating incubator; 13-Esophageal eccentric convex wheel; 14-Esophageal fixed concave wheel; 15- gastric eccentric concave wheel; 16-Eccentric flat wheel of stomach; 17-duodenal eccentric concave wheel; 18-Fixed convex wheel of

17678736_1 duodenum; 19-Stomach extrusion device; 20-Pylorus clamp; 21-Funnel support base; 22-Peristaltic pump for stomach digestive juice; 23-Gastric juice tank; 24-Gastric juice inlet tube; 25-Peristaltic pump for pancreatic digestivejuice; 26-Pancreatic juice tank; 27-Pancreatic juice inlet tube; 28-Peristaltic pump for bile digestive juice; 29-Bile tank; 30-Bile inlet tube; 31-Peristaltic pump for emptying; 32-Emptying tube; 33-Synchronous shaft I; 34-Eccentric shaft I; 35-Bearing I; 36-Cam I; 37-Fixed shaft I; 38-Concentric shaft I; 39-Concave wheel I; 40-Synchronous shaft II; 41-Eccentric shaft II; 42-Bearing II; 43-Concave wheel II; 44-Synchronous shaft III; 45-Eccentric shaft III;46 -Bearing III; 47- Fixed shaft II; 48 Concentric shaft II; 49-Cam II; 50- Transition plate; 51- Extrusion head mounting position (not mounted); 52- Extrusion head mounting position (mounted); 53- Extrusion motherboard; 54 Extrusion push rod; 55- Extrusion head; 56- Rear extrusion plate, 561- Trapezoidal convex structure; 57- Front extrusion plate, 571- Trapezoidal concave structure; 58- Pylorus push rod; 59- Driving motor; 60- Connecting device; 61- Funnel; 70- Plexiglas sheet, 701- Smooth holes; 80- Secretion tube. DETAILED DESCRPTION A clear and complete description of the technical solution of the present disclosure is given below in conjunction with the attached drawings. It is evident that the examples described herein is merely partial examples rather than all examples of the present disclosure. All other examples obtained by those skilled in the art based on examples in the present disclosure without making creative labor fall within the scope of protection in the present disclosure. As set forth as Figure 1, the present disclosure provides a method for fabricating an integrated model of flexible human esophagus, stomach, duodenum and small intestine, comprising the following steps:

[Sl] Scanning the internal and external structures of human esophagus, stomach, duodenum

and small intestine to prepare an esophagus mold a, a stomach mold b, a duodenum mold c and a small intestine mold d; Three-dimensional scanner is used to scan the internal and external structures of human esophagus, stomach and duodenum, respectively, and the scanned image is modeled and saved into a picture in STL format through three-dimensional modeling software; the three-dimensional image is input into a 3D printer, and human esophagus mold, stomach mold and duodenum mold are prepared in turn.

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Preparation of esophagus mold: Based on the esophageal physiological data of real human, it is determined that the esophagus has an average outer diameter of 20 mm and an average inner diameter of 15.6 mm, and that there are three strictures in the esophagus, the first stricture is at the origin of the esophagus, namely at the junction between pharynx and esophagus; the second stricture is 7 cm below the inlet of the esophagus; and the third stricture is at the junction between esophagus and stomach. According to the inner diameter and outer diameter dimensions of the esophagus, a mold of a flat silicone plate is first fabricated, and the length of the inner slot of this mold is 250 mm and the width of the inner slot of this mold is K * outer diameter of the esophagus = 62.8 mm. The required silicone volume is 250 x 62.8 x 2.2 mm3 = 345.4ml. Method for preparing the stomach mold: A 3D scanner is used to scan the internal and external structures of the real stomach, 3D reconstruction is performed with 3D modeling software, and the mold is saved into STL format identified by 3D printer. The mold is printed layer by layer using a 3D printer. Stomach mold is composed of four parts, including an internal mold and an external mold, wherein the internal mold and the external mold are assembled from two parts respectively. The method for preparing the duodenum mold: The internal and external structures of the real duodenum of human are scanned using a three-dimensional scanner; based on duodenum data of real human, the duodenum can be determined to have an outer diameter of 70 mm, an inner diameter of 50 mm, and a circumferential fold cI. According to the inner diameter and outer diameter dimensions of the duodenum, a mold of a flat silicone plate is first fabricated, and the length of the inner slot of this mold is 250 mm and the width of the inner slot of this mold ist * outer diameter of the duodenum= 219.8 mm. The

required silicone volume is 250 x219.8 x10 mm3 = 549.5ml.

Method for preparing small intestine mold: According to the structural sizes of the small intestine of real human as obtained by the three-dimensional scanner, small smooth holes 701 with certain interval, diameter and depth are punched on the perspex sheet 70 to prepare the small intestine mold.

[ S2] Applying a mold release agent evenly on the molds, pouring elastic liquid material on the

17678736_1 molds, then releasing the molds after their curing to obtain esophagus model, stomach model, duodenum model and small intestine model, and performing drying after surface cleaning; Preparation of silicone rubber liquid: Calculate the space reserved between the internal and external molds of the fabricated mold as well as the volume of biomimetic human esophagus, stomach, duodenum and small intestine to be manufactured, prepare the liquid silicone, and mix and debubble the liquid silicone and cross-linking agent to obtain the un-crosslinked liquid silicone. The volume of pouring liquid is equal to the volume of soft elastic container material to be manufactured. Of course, the present disclosure can also adopt other elastomer materials. The mechanical performance parameters of silicone material: tensile strength of 40 kgf/cm, elongation at break of 300 - 600%, tensile strength of 20 - 30 kgf/cm and linear shrinkage of <

0.5%. Wherein the method for preparing the esophagus model and the duodenum model: according to the inner and outer diameter dimensions of human esophagus and duodenum obtained by three-dimensional scanning, the esophagus mold and the duodenum mold with a flat silicone plate structure are respectively made using the silicone material, the lengths of the molds are respectively equal to the length of esophagus and the length of duodenum, and the widths of the molds are equal to the outer diameter perimeter of the esophagus and that of the duodenum; the two silicone plates are coated with the binding agent layer by layer along both sides in their length directions, and the esophagus model and the duodenum model are respectively prepared after curing. The method for preparing the small intestine model concretely comprises the following steps: molding smooth holes 701 with certain interval, diameter and depth on the perspex sheet 70 to prepare the small intestine mold; applying a mold release agent on the mold of perspex sheet 70, pouring an elastic liquid material on the small intestine mold, releasing the mold after curing, and drying the mold after surface cleaning to prepare the preliminary model of small intestine; the preliminary model of small intestine is coated with binding agent layer by layer along both sides in its length direction, and the small intestine model is prepared after curing. The method for preparing the stomach model comprises the following steps: using a 3D printer to print the internal and external models of the stomach mold according to the internal and external dimensions of human stomach as obtained through three-dimensional scanning;

17678736_1 applying a mold release agent to the external surface of the internal model and the internal surface of the external model, respectively; pouring an elastic liquid material into the gap formed by the internal model and the external model, after curing, the left and right stomach models are prepared by demolding, and are dried after surface cleaning; applying a binding agent layer by layer on both sides of the dried stomach model along its length direction; after curing, the stomach model is prepared. Mixing the silicone rubber at a mass ratio of 1:1, and making vacuum-pumping for 10 min until all bubbles have disappeared. At the same time, wash clean each mold, evenly coat mold release agent on each mold, and then fill each mold according to the required amount, in which esophageal mold, duodenal mold and small intestine mold are filled according to the required amount, and stomach mold is filled (about 650 ml). Place the molds filled with silicone rubber in an oven with temperature lower than 400for drying for 3 hours, and then take out the molds to obtain the corresponding models.

[S3] Punching holes in the stomach model, duodenum model and small intestine model, respectively, inserting and fixing a flexible tube in the holes as a secretion tube 80; Preferably, the secretion tube is a silicone tube with an outer diameter of 2 mm, an inner diameter of 1 mm and a length of 300 - 400 mm. Use a puncher to punch holes on the prepared stomach model, duodenum model and small intestine model, insert the silicone tubes into the holes and use the glue to bond them; the silicone tube can protrude a part; After they have been well adhered, cut evenly the silicone tubes along the stomach wall. At the same time, ensure that the silicone tubes are not blocked by glue, and the ports at the insertion ends do not exceed the internal surfaces of stomach model, duodenum model and small intestine model. Place the silicone tubes for 3 h after bonding, and then respectively introduce water-soluble red liquid dye into each silicone tube, and inspect the conduction of secretion tube. Then, integrate the gastric secretion tubes into a thick tube, and use a solid wire with certain length to block each silicone tube in advance, so as to prevent glue from flowing into the secretion tube. After bonding, remove the tubes, and introduce water-soluble red liquid dye into the tubes to inspect whether there is liquid leakage and/or blockage. Apply silicone binding agent layer by layer on the joints of both sides along the length direction of each model, with the curing duration for each layer of silicone binding agent being 2.5 - 3.5

17678736_1 hours, and apply 5 - 7 layers; seal the outlet at one end of mold and inject water-soluble red liquid fuel from the other end to detect whether there is liquid leakage from the mold. 12 holes are punched on each of two sides of the stomach wall of the stomach model using a puncher with diameter of 5 mm, at least one hole is punched at the position of major papilla of the duodenum model and the small intestine model, the secretion tubes are fixed in the corresponding holes one by one, the insertion end port of the secretion tubes does not exceed the inner surface of the stomach model and the duodenum model, and is communicated with the inner surface of the stomach model and the duodenum model.

[ S4 ] Adhesive is used to bond biomimetic human esophagus model, stomach model,

duodenum model and small intestine model in the order of structures to obtain an integrated model, and an examination on fluid leakage is also made. As set forth as Figure 4, the present disclosure provides a dynamic human stomach-duodenum in vitro biomimetic digestive system, which comprises a heating incubator 12 as well as an esophagus model a, a stomach model b, a duodenum model c, a peristaltic extrusion device and a digestion and emptying unit which are located in the heating incubator 12, wherein the esophagus model a, the stomach model b and the duodenum model c are connected with each other; the peristaltic extrusion device is respectively arranged on both sides of the esophagus model a, the stomach model b and the duodenum model c to realize the biomimetic movement of the esophagus model a, the stomach model b and the duodenum model c; the digestion and emptying unit comprises a feeding device connected with the inlet of the esophagus mode a, a digestive juice adding device connected with the stomach model b and the duodenum model c and an emptying device connected with the outlet end of the duodenum model c; Preferably, the esophagus model a, the stomach model b, and the duodenum model care models made from silicone, and detachably and fixedly connected to each other. Of course, the models can also be made of other flexible materials. Of course, the present disclosure may also add an adjusting device in the system, as set forth as Figure 12, the adjusting device for the placement angle of the digestive system is composed of a driving motor 59 and a connecting device 60, wherein the connecting device 60 is designed to connect the shaft of the driving motor 59 with the incubator body of the heating incubator 12. When driving motor 59 is rotating, power is transmitted to the heating incubator 12 through connecting device 60 to realize the rotation of heating incubator 12;

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As set forth as Figure 3, the present disclosure models the real human esophagus -stomach - and duodenum according to the size ratio of 1:1 to prepare an human esophagus model a, a stomach model b and a duodenum model c. The sizes, shapes and internal physiological structures of these models are consistent with those of real human esophagus, stomach and duodenum. These models are soft but have high elasticity and tear resistance. In the present disclosure, the esophagus model a is connected with the stomach model b and the duodenum model c in a detachable manner; as set forth as Figure 3, there are three temperature measurement points on the human esophagus model a-stomach model b-duodenum model c, and the temperature measurement elements 1, 2 and 3 are installed at these three temperature measurement points, namely, the temperature measurement element 1 distributed at the inlet of the esophagus model a, the temperature measurement element 2 distributed at the inlet of the stomach model b and the temperature measurement element 3 distributed at the inlet of the duodenum model c. For the purpose of temperature measurement, a thermocouple wire (0.5 mm wire diameter) is used as the temperature measurement element, and the temperature data is collected and recorded on the computer in real time; there are also 3 pH measurement points provided on the human esophagus model a-stomach model b-duodenum model c. pH acquisition elements are respectively installed at these 3 positions for measuring pH values, namely the pH acquisition element 7 specifically distributed at the front end of the stomach model a, the pH acquisition element 8 distributed at the rear end of the pylorus, and the pH acquisition element 9 distributed at the outlet of the duodenum model c. For the purpose of pH measurement, a small pH meter is used to collect and record pH data on the computer in real time; meanwhile, multiple gastric juice inlets 4 are arranged on the front and rear sides of the stomach model a to ensure the even distribution of gastric juice in the stomach; a bile inlet 5 and a pancreatic juice inlet 6 are arranged at the front end of duodenum model c to respectively inject bile and pancreatic juice into the duodenum model c. The key components used to achieve squeezing peristalsis of the esophagus model a, the stomach model b, and the duodenum model c are described below. As set forth as Figure 4, the peristalsis extrusion device is a peristaltic device designed to realize the biomimetic movement of the esophagus model a, stomach model b, and duodenum model c; the peristalsis of the esophagus model a is achieved by the combined action of the esophageal eccentric convex wheel 13 and the esophageal fixed concave wheel 14; the peristalsis of the

17678736_1 stomach is achieved by the combined action of the gastric eccentric concave wheel 15 and the gastric eccentric flat wheel 16; the peristalsis of the duodenum model c is achieved by the combined action of the duodenal eccentric concave wheel 17 and the duodenal fixed convex wheel 18; the opening and closing of the pylorus is achieved by the pyloric clamp 20. As set forth as Figure 4, the present disclosure also provides a stomach extrusion device 19 which is designed to enable the stomach realize forward and backward extrusion motion, wherein its extrusion direction is vertical to the direction of peristaltic action force of the peristaltic device, and it is set on both sides of the stomach model b; as set forth as Figures 10a, 1Ob and 1Oc, the stomach extrusion device 19 comprises an extrusion push rod 54, an extrusion motherboard 53 and multiple groups of extrusion heads 55; the extrusion push rod 54 is fixedly connected with the extrusion motherboard 53 through the transition plate 50 to drive the reciprocating motion of the extrusion motherboard 53, and the multiple groups of extrusion heads 55 are vertically arranged on the extrusion motherboard 53 to form a thread connection with the extrusion motherboard 53. The stretching movement of the extrusion push rod 54 drives the extrusion motherboard 53 to perform the forward and backward movement, and the stretching frequency, speed and stroke of the extrusion push rod 54 are adjustable; on the extrusion motherboard 53, many extrusion head mounting positions 51 and 52 are distributed according to the shape of stomach model b, and the extrusion head mounting positions 51 and 52 are threaded holes; one end of the extrusion head 55 is a semicircular structure used for squeezing the stomach model b, and the other end is a threaded columnar structure designed to adjust the longitudinal distance on the extrusion head mounting positions 51 and 52. The number and positions of extrusion heads 55 can be adjusted according to the position of gastric juice inlet 4 as well as the experimental conditions, etc. As set forth as Figure 4 and Figure 11, the pylorus below the stomach model b is also provided with a pylorus clamp 20 having the same action force as the stomach extrusion device 19. The pylorus clamp 20 is composed of a front extrusion plate 57, a rear extrusion plate 56 and a pylorus pushing rod 58; the pylorus push rod 58 is telescopic to drive the front extrusion plate 57 to make the forward and backward movement; the stretching frequency, speed and stroke of pylorus pushing rod 58 are adjustable; the front extrusion plate 57 is designed as a trapezoidal convex structure 571; the rear extrusion plate 56 is designed as a trapezoidal concave structure 561; the front extrusion plate 57 and the rear extrusion plate 56 can fully engaged.

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As set forth as Figure 4, the heating incubator 12 comprises an incubator body 11, a heating lamp 10 set inside the incubator body 11, and a temperature control device; the heating lamp 10 includes an upper layer heating lamp 101 of the incubator and a lower layer heating lamp 102 of the incubator, which are used to provide the temperature for the biomimetic organs, respectively. The heating lamp 10 is controlled by the temperature control device; the incubator body 11 is made of perspex structure, which has a certain heat preservation effect under the premise of ensuring visualization; the front, left and right doors of the heating incubator 12 can be opened to facilitate operation. As set forth as Figure 4 and Figure 5a and Figure 5b, the esophageal eccentric cam 13 is composed of a synchronous shaft 133, an eccentric shaft 134, a bearing 135 and a cam 136; the synchronous shaft 133 and drive motor shaft are connected through synchronous belt; the eccentric shaft 134 enables the cam 136 to make eccentric movement; bearing 135 is fastened on the outer side of the eccentric shaft 134 and the inner side of the cam 136, so as to ensure that the cam 136 has drum friction rather than sliding friction when having contact with the esophagus model a and will not pull down the esophagus model a; the smooth surface of nylon material on the lateral side of cam136 can prevent cutting damage to the esophagus model a; the arc-shaped convex of cam 136 is engaged with the arc-shaped recess of the esophageal fixed concave wheel 14. As set forth as Figures 6a and 6b, the esophageal fixed concave wheel 14 is composed of a fixed shaft 137, a coaxial shaft 138 and a concave wheel 139; the fixed shaft 137 is fixed on a supporting plate; the coaxial shaft 138 is internally connected with the fixed shaft 137 and is externally connected with the concave wheel 139; the smooth surface of nylon material adopted on the concave wheell39 can prevent the esophagus model a from being cut; the concave surface structure of the concave wheel 139 can effectively hold the esophagus and prevent the esophagus model a from sliding out when it is squeezed; the arc-shaped recess of the concave wheel 139 is engaged with the arc-shaped convex of the esophageal eccentric convex wheel 13. As set forth as Figure 4, Figure 7a and Figure 7b, the gastric eccentric concave wheel 15 and the duodenal eccentric concave wheel 17 are composed of a synchronous shaft 1140, an eccentric shaft 1141, a bearing 1142 and a concave wheel 1143; the synchronous shaft 1140 is connected with the driving motor shaft through synchronous belt; the eccentric shaft 1141 enables the concave wheel 1143 to make eccentric motion; the bearing 1142 is fastened on the outer side of

17678736_1 the eccentric shaft 1141 and the inner side of the concave wheel 1143, so that the concave wheel 1143 has drum friction rather than sliding friction when having contact with the stomach model b and the duodenum model c, and thus will not pull down the stomach model b and the duodenum model c; the smooth surface of nylon material adopted on the concave wheel1143 can prevent the stomach model b and the duodenum model c from being cut. The concave surface structure of the concave wheel 1143 can effectively hold the stomach model b and the duodenum model c and thus prevent them from sliding out when they are squeezed; the arc-shaped recess of the concave wheel 1143 is engaged with the arc-shaped convex of the duodenal fixed convex wheel 18. As set forth as Figure 4, Figure 9a and Figure 9b, the gastric eccentric flat wheel 16 is composed of a synchronous shaft11144, an eccentric shaft11145, and a bearing 11146; the synchronous shaft 11144 and drive motor shaft are connected through synchronous belt; the eccentric shaft11145 enables the bearing 11146 to make eccentric movement; the bearing 11146 is fastened on the outer side of the eccentric shaft 11145 to ensure that the outer wheel of bearing 11146 has drum frication rather than sliding frication when having contact with the stomach model b and does not pull down the stomach model a. As set forth as Figures 4, 8a and 8b, duodenal fixed convex wheel 18 is composed of a fixed shaft 1147, a concentric shaft 1148 and a cam 1149; the fixed shaft 1147 is fixed on the supporting plate, and the concentric shaft 1148 is connected with the fixed shaft 1147 and the cam1149; the smooth surface of the cam 1149 made from nylon material can prevent the duodenum model c from being cut. As set forth as Figure 13, the feeding device comprises a funnel supporting base 21 and a funnel 61, wherein the funnel supporting base 21 is arranged above the outside of the heating incubator 12, the lower end of the funnel 61 is communicated with the inlet of the esophagus model a, and food can be injected into the esophagus model a through the funnel 61. At least three groups of the digestive juice adding devices are provided, wherein the digestive juice adding device comprises liquid tanks 23, 26 and 29, digestive juice peristaltic pumps 22, 25 and 28, and juice inlet pipes 24, 27 and 30, wherein the juice tanks were gastric juice tank 23, pancreatic juice tank 26, and bile tank 29, respectively, and the digestive juice peristaltic pumps are gastric digestive juice peristaltic pump 22, pancreatic digestive juice peristaltic pump 25, and bile digestive juice peristaltic pump 28, respectively, the inlet tubes are gastric juice inlet tube 24,

17678736_1 pancreatic juice inlet tube 27, and bile inlet tube 30, respectively, the inlets of digestive juice peristaltic pumps 22, 25, and 28 are connected to the corresponding juice tanks 23, 26, and 29, respectively, and the outlets of digestive juice peristaltic pumps 22, 25, and 28 are connected to the corresponding one end ofjuice inlet tubes 24, 27, and 30, the other end of each ofjuice inlet tubes 24, 27, 30 is connected to the bile inlet 5, pancreatic juice inlet 6, and multiple gastric juice inlet 4 on the corresponding stomach model b and duodenum model c, respectively. The emptying device comprises an emptying peristaltic pump 31 and an emptying tube 32 connected to the emptying peristaltic pump 31, wherein the emptying tube 32 is connected to the outlet end of the duodenum model c. 4 peristaltic pumps are provided for adding gastric juice, bile, pancreatic juice and for assisting food emptying, respectively; 3 juice tanks 23, 26 and 29 are provided for containing gastric juice, pancreatic juice and bile respectively; 4 groups of juice inlet tubes 24, 27, 30 and 32 are provided for adding gastric juice, pancreatic juice and bile and for emptying food respectively; gastric juice tube 24 is divided into multiple branch tubes from a main tube, wherein one end of each branch tube is connected with the main tube, and the other end of each branch tube is connected with the gastric juice inlet 4 on the stomach wall. Set the temperature of the upper and lower layers of the heating incubator on the operating panel; adjust the relative angles of the eccentric wheels on the esophagus model, the stomach model and the duodenum model; set the speed of each wheel on the operating panel, set the extrusion frequency, speed and depth of the stomach extrusion device, and set the opening and closing frequency and speed of the pylorus; add food to the funnel and start the peristaltic pump to inject gastric juice, bile and pancreatic juice. The food enters the esophagus through the funnel, and enters the stomach through the roller peristalsis on the esophagus and the regulation of temperature by the heating lamp; the food is fully mixed with gastric juice after being squeezed through the peristalsis of stomach, and the physical size of food becomes smaller under the action force of peristalsis and squeezing; the broken small-size food enters the duodenum through the narrow suture of pylorus; the small-size food is fully mixed with bile and pancreatic juice after being squeezed through the peristalsis of duodenum, and the size of food is further reduced to a certain extent; the food is discharged from the terminal of duodenum under the action force of assisted emptying peristaltic pump. The technical means disclosed in the solution of the present disclosure are not only limited to

17678736_1 the technical means disclosed in the said technical means, but also include technical solutions composed of any combination of said technical features. It is obvious that the above-mentioned examples are merely examples given for the purpose of clearly describing rather than limiting the detailed description. For those skilled in the art, it is feasible to make changes or alterations in different forms on the basis of the above description. Here, it is neither necessary nor possible to exhaust all detailed descriptions. The obvious changes or modifications thereby derived still fall within the scope of protection of the present disclosure. It is to be understood that, if any prior art is referred to herein, such reference does not constitute an admission that the prior art forms a part of the common general knowledge in the art, in Australia or any other country. In the claims which follow and in the preceding description of the invention, except where the context requires otherwise due to express language or necessary implication, the word "comprise" or variations such as "comprises" or "comprising" is used in an inclusive sense, i.e. to specify the presence of the stated features but not to preclude the presence or addition of further features in various embodiments of the invention.

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Claims

1. A method for preparing an integrated model of flexible human esophagus, stomach, duodenum and small intestine, wherein the method comprises the following steps:

step 1: scanning the internal and external structures of a human esophagus, a stomach, a duodenum and a small intestine by using a 3D scanner to prepare an esophagus mold, a stomach mold, a duodenum mold and a small intestine mold;

step 2: applying a mold release agent evenly on the molds, pouring elastic liquid material on the molds, then releasing the molds after their curing to obtain an esophagus model, a stomach model, a duodenum model and a small intestine model with a size ratio of 1:1 with the real human stomach, the esophagus, the duodenum and the small intestine respectively, and performing drying after surface cleaning;

step 3: punching holes in the stomach model, the duodenum model and the small intestine model, respectively, inserting and fixing a flexible tube in the holes as a secretion tube;

step 4: using an adhesive to bond the biomimetic human esophagus model, the stomach model, the duodenum model and the small intestine model in the order of structures to obtain an integrated model.

2. The preparation method of claim 1, wherein in the step 1, scanned images of the internal and external structures of the human esophagus, the stomach and the duodenum, respectively, are modeled and saved into pictures in STL format through a three-dimensional modeling software; the three-dimensional images are input into a 3D printer, and the human esophagus mold, the stomach mold and the duodenum mold are successively prepared.

3. The preparation method of claim 1, wherein the method for preparing the esophagus model and the duodenum model comprises the following steps: according to the inner and outer diameter dimensions of the human esophagus and the duodenum obtained by three-dimensional scanning, the esophagus mold and the duodenum mold with a flat silicone plate structure are respectively made using the silicone material, the lengths of the molds are respectively equal to the length of esophagus and the length of duodenum, and the widths of the molds are equal to the outer diameter perimeter of the esophagus and that

17678736_1 of the duodenum; the two silicone plates are coated with the binding agent layer by layer along both sides in their length directions, and the esophagus model and the duodenum model are respectively prepared after curing.

4. The preparation method of claim 1, wherein the method for preparing the small intestine model comprises the following steps: molding smooth holes with certain interval, diameter and depth on a sheet to prepare the small intestine mold; applying a mold release agent on the sheet mold, pouring an elastic liquid material on the small intestine mold, releasing the mold after curing, and drying the mold after surface cleaning to prepare the preliminary model of small intestine; the preliminary model of the small intestine is coated with binding agent layer by layer along both sides in its length direction; the small intestine model is prepared after curing.

5. The preparation method of claim 1, wherein the method for preparing the stomach model comprises: using a 3D printer to print the internal and external models of the stomach mold according to the internal and external dimensions of human stomach as obtained through three-dimensional scanning; applying a mold release agent to the external surface of the internal model and the internal surface of the external model, respectively; pouring an elastic liquid material into the gap formed by the internal model and the external model, after curing, the left and right stomach models are prepared by demolding, and are dried after surface cleaning; applying a binding agent layer by layer on both sides of the dried stomach model along its length direction; after curing, the stomach model is prepared.

6. The preparation method of any one of claims 2-5, wherein applying silicone binding agent layer by layer on the joints of both sides along the length direction of each model after drying, with the curing duration for each layer of silicone binding agent being 2.5 - 3.5 hours, and apply 5 - 7 layers; sealing the outlet at one end of mold and injecting water-soluble red liquid fuel from the other end to detect whether there is liquid leakage from the mold.

7. The preparation method of claim 6, wherein the secretion tube used in step 3 is a silicone tube with an outer diameter of 2 mm, an inner diameter of 1 mm and a length of 300 - 400 mm.

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8. The preparation method of claim 6, wherein in the step 3, 12 holes are punched on each of two sides of the stomach wall of the stomach model using a puncher with diameter of 5 mm, at least one hole is punched at the position of major papilla of the duodenum model, the secretion tubes are fixed in the corresponding holes one by one, the insertion end port of the secretion tubes does not exceed the inner surface of the stomach model and the duodenum model, and is communicated with the inner surface of the stomach model and the duodenum model.

9. The preparation method of claim 8, wherein the elastic liquid material used is silicone material with tensile strength of 4-6 kgf/cm 2 , elongation at break of 300-800%, tensile strength of 20-30 kgf/cm 2 and linear shrinkage of < 0.5%.

10. A dynamic in vitro biomimetic digestive system, wherein the digestive system comprises a heating incubator as well as an esophagus model, a stomach model, a duodenum model, a peristaltic extrusion device and a digestion and emptying unit which are located in the heating incubator, wherein the esophagus model, the stomach model and the duodenum model are soft models, made by pouring elastic liquid material on an esophagus mold, a stomach mold and a duodenum mold respectively, obtained by scanning the internal and external structures of a human esophagus, a stomach and a duodenum by using a 3D scanner, and then releasing the molds after the elastic liquid material curing, and have a size ratio of 1:1 with the real human stomach, the esophagus and the duodenum respectively, and the esophagus model, the stomach model and the duodenum model are connected with each other; the peristaltic extrusion device is respectively arranged on both sides of the esophagus model, the stomach model and the duodenum model to realize the biomimetic movement of the esophagus model, the stomach model and the duodenum model; the digestion and emptying unit comprises a feeding device connected with the inlet of the esophagus model, a digestive juice adding device connected with the stomach model and the duodenum model and an emptying device connected with the outlet end of the duodenum model; and

the food enters the esophagus model through the feeding device, and the food sequentially enters the stomach model and the duodenum model under the action of the peristaltic extrusion device; wherein the digestive juice in the digestive juice adding device enters the

17678736_1 stomach model and the duodenum model, and is mixed with the food, wherein the food is excreted by the emptying device after the food digestion is completed.

11. The dynamic in vitro biomimetic digestive system of claim 10, wherein the esophagus model, the stomach model, and the duodenum model are silicone models which are detachable and fixedly connected to each other.

12. The dynamic in vitro biomimetic digestive system of claim 10, wherein the esophagus model, the stomach model, and the duodenum model are respectively provided with temperature measuring elements and pH collecting elements; wherein the temperature measuring elements are respectively distributed at the inlet of the esophagus module, the inlet of the stomach model and the inlet of the duodenum model; the pH collecting elements are arranged at the pylorus below the stomach model and the outlet of the duodenum model; the temperature measuring elements and the pH collecting elements are connected with the computer to realize data connection.

13. The dynamic in vitro biomimetic digestive system of claim 10, wherein the stomach model is provided with a plurality of gastric juice inlets on both its front and rear sides, and the front part of the duodenum model is provided with a bile inlet and a pancreatic juice inlet; the digestive juice adding device is respectively connected with the gastric juice inlet, the bile inlet and the pancreatic juice inlet for injecting gastric juice, bile and pancreatic juice into the stomach model and the duodenal model respectively.

14. The dynamic in vitro biomimetic digestive system of claim 10, wherein the peristaltic extrusion device comprises a peristaltic device for driving the esophagus model, the stomach model and the duodenum model to produce biomimetic peristalsis, respectively, wherein the peristaltic device comprises multiple sets of esophageal eccentric convex wheels and esophagus fixed concave wheels engaged on both sides of the esophagus model, multiple sets of stomach eccentric concave wheels and stomach eccentric flat wheels on both sides of the stomach model, and multiple sets of duodenum eccentric concave wheels and duodenum fixed convex wheels on both sides of the duodenum model; the eccentric convex wheels, the eccentric concave wheels and the eccentric flat wheels are respectively driven to rotate by a driving motor.

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15. The dynamic in vitro biomimetic digestive system of claim 14, wherein the peristaltic extrusion device also comprises a stomach extrusion device whose extrusion direction is perpendicular to the peristaltic action force direction of the peristaltic device, wherein the stomach extrusion device is arranged on both sides of the stomach model and comprises a extrusion push rod, an extrusion motherboard and a plurality of groups of extrusion heads; the extrusion push rod is fixedly connected with the extrusion motherboard to drive the extrusion motherboard to make reciprocating movement, and the plurality of groups of extrusion heads are vertically arranged on the extrusion motherboard to form threaded connection with the extrusion motherboard.

16. The dynamic in vitro biomimetic digestive system of claim 15, wherein the pylorus position below the stomach model is also provided with a pylorus clamp having the same action force as the stomach extrusion device, wherein the pylorus clamp comprises a front extrusion plate, a rear extrusion plate and a pylorus push rod; wherein the pylorus push rod is fixedly connected with the front extrusion plate to drive the front extrusion plate to make reciprocating movement, wherein a trapezoidal convex structure is molded on the rear extrusion plate; a trapezoidal concave structure is molded on the front extrusion plate; the front extrusion plate and the rear extrusion plate form complete engagement.

17. The dynamic in vitro biomimetic digestive system disclosed in any one of claims 10-16, wherein the heating incubator comprises an incubator body, a heating lamp arranged inside the incubator body and a temperature control device; the heating lamp is used to provide temperature for the biomimetic organs, and the heating lamp is electrically connected with the temperature control device to control the heating temperature of the heating lamp.

18. The dynamic in vitro biomimetic digestive system of claim 17, wherein the digestive system is also provided with an adjusting device for adjusting the placement angle of the heating incubator, which comprises a driving motor and a connecting device, wherein the connecting device is designed to connect the driving motor to the heating incubator; and the angle of the heating incubator is adjusted through the leftward and rightward rotation of the driving motor.

19. The dynamic in vitro biomimetic digestive system of claim 18, wherein the feeding device

17678736_1 comprises a funnel supporting base and a funnel, wherein the funnel supporting base is arranged above the outside of the heating incubator, and the lower end of the funnel is communicated with the inlet of the esophagus model.

20. The dynamic in vitro biomimetic digestive system of claim 19, wherein at least three groups of the digestive juice adding devices are provided, wherein the digestive juice adding devices comprisejuice tanks, digestivejuice peristaltic pumps andjuice inletpipes, the juice inlet of each of digestive juice peristaltic pumps is correspondingly connected with each of corresponding juice tanks, the juice outlet of each of the digestive juice peristaltic pumps is correspondingly connected with one end of each of the juice inlet pipes, and the other end of each of the juice inlet pipes is respectively connected with the corresponding bile inlet, pancreatic juice inlet and multiple gastric juice inlets on the stomach model and the duodenum model.

21. The dynamic in vitro biomimetic digestive system of claim 20, wherein the emptying device comprises an emptying peristaltic pump and an emptying tube connected to the emptying peristaltic pump, wherein the emptying tube is connected to the outlet end of the duodenum model.

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