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WO2020062521A1 - 一种仿生消化道及其制备方法和应用 - Google Patents

一种仿生消化道及其制备方法和应用 Download PDF

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Publication number
WO2020062521A1
WO2020062521A1 PCT/CN2018/117135 CN2018117135W WO2020062521A1 WO 2020062521 A1 WO2020062521 A1 WO 2020062521A1 CN 2018117135 W CN2018117135 W CN 2018117135W WO 2020062521 A1 WO2020062521 A1 WO 2020062521A1
Authority
WO
WIPO (PCT)
Prior art keywords
bionic
mold
jejunum
duodenum
human
Prior art date
Application number
PCT/CN2018/117135
Other languages
English (en)
French (fr)
Inventor
詹晓北
李志涛
高敏杰
张文龙
徐静静
蒋芸
Original Assignee
江南大学
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from CN201811143752.8A external-priority patent/CN109192031B/zh
Priority claimed from CN201811143735.4A external-priority patent/CN108943518B/zh
Priority claimed from CN201811143745.8A external-priority patent/CN109333881B/zh
Priority claimed from CN201811143746.2A external-priority patent/CN109333882B/zh
Priority claimed from CN201811143747.7A external-priority patent/CN109333883B/zh
Application filed by 江南大学 filed Critical 江南大学
Publication of WO2020062521A1 publication Critical patent/WO2020062521A1/zh
Priority to US16/875,106 priority Critical patent/US11721241B2/en
Priority to US18/325,338 priority patent/US12131665B2/en

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Classifications

    • G—PHYSICS
    • G09—EDUCATION; CRYPTOGRAPHY; DISPLAY; ADVERTISING; SEALS
    • G09B—EDUCATIONAL OR DEMONSTRATION APPLIANCES; APPLIANCES FOR TEACHING, OR COMMUNICATING WITH, THE BLIND, DEAF OR MUTE; MODELS; PLANETARIA; GLOBES; MAPS; DIAGRAMS
    • G09B23/00—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes
    • G09B23/28—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes for medicine
    • G09B23/30—Anatomical models
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C39/00—Shaping by casting, i.e. introducing the moulding material into a mould or between confining surfaces without significant moulding pressure; Apparatus therefor
    • B29C39/02—Shaping by casting, i.e. introducing the moulding material into a mould or between confining surfaces without significant moulding pressure; Apparatus therefor for making articles of definite length, i.e. discrete articles
    • B29C39/026—Shaping by casting, i.e. introducing the moulding material into a mould or between confining surfaces without significant moulding pressure; Apparatus therefor for making articles of definite length, i.e. discrete articles characterised by the shape of the surface
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29B—PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
    • B29B13/00—Conditioning or physical treatment of the material to be shaped
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C33/00—Moulds or cores; Details thereof or accessories therefor
    • B29C33/38—Moulds or cores; Details thereof or accessories therefor characterised by the material or the manufacturing process
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C39/00—Shaping by casting, i.e. introducing the moulding material into a mould or between confining surfaces without significant moulding pressure; Apparatus therefor
    • B29C39/22—Component parts, details or accessories; Auxiliary operations
    • B29C39/26—Moulds or cores
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C41/00—Shaping by coating a mould, core or other substrate, i.e. by depositing material and stripping-off the shaped article; Apparatus therefor
    • B29C41/02—Shaping by coating a mould, core or other substrate, i.e. by depositing material and stripping-off the shaped article; Apparatus therefor for making articles of definite length, i.e. discrete articles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29B—PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
    • B29B13/00—Conditioning or physical treatment of the material to be shaped
    • B29B2013/005—Degassing undesirable residual components, e.g. gases, unreacted monomers, from material to be moulded
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2083/00—Use of polymers having silicon, with or without sulfur, nitrogen, oxygen, or carbon only, in the main chain, as moulding material
    • B29K2083/005—LSR, i.e. liquid silicone rubbers, or derivatives thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2091/00—Use of waxes as moulding material
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2105/00—Condition, form or state of moulded material or of the material to be shaped
    • B29K2105/0058—Liquid or visquous
    • B29K2105/0061—Gel or sol
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29L—INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES
    • B29L2031/00—Other particular articles
    • B29L2031/753—Medical equipment; Accessories therefor
    • B29L2031/7532—Artificial members, protheses

Definitions

  • the invention relates to a bionic digestive tract, a preparation method and application thereof, and belongs to the field of bionic technology and biotechnology.
  • Human digestive tract in vitro simulation devices are bionic simulation devices for the human digestive system and its digestive environment, and the dynamic behavior of fluids in the digestive tract, which can simulate different samples in an in vitro model The digestion process and the effect of these samples on intestinal microorganisms, so as to provide a lot of valuable data for the development of new functional foods. If it is used as a "pre-test" to predict the living test, it can completely or partially replace the living test. To achieve the purpose of reducing costs and time, improving repeatability and accuracy, and there is no theoretical limit.
  • the human digestive tract in vitro simulation device is becoming more and more critical in the research of food, drugs, and even microorganisms, which provides great convenience for the research of food science and human nutrition. It is unmatched by mouse experiments or human volunteer experiments. of.
  • the simulated digestive tract (mainly including the stomach, small intestine, and large intestine) is the main body of a human digestive tract in vitro simulation device.
  • the degree of simulation of the human real digestive tract is very important in the simulation performance of the entire human digestive tract in vitro simulation device.
  • the internal physiological structures of the existing digestive tract models made of silicone and latex are smooth and do not have the function of grinding food. They can only realistically simulate some liquid foods (drinks, milk, etc.) that do not need to be ground. Digestive status in the stomach; for solid (rice, fruit, meat, etc.) or semi-solid (congee, soup, etc.) foods, they can only reflect the function of mixed foods, and they cannot truly reflect the gastrointestinal tract grind and digest food Functions.
  • these digestive tract models are often simply made into an overall structure. For example, they can be molded into a stomach with silicone or latex at one time. These stomachs cannot simulate the "backflow" function between the gastric antrum and the stomach body, resulting in The experimental measurement results are not accurate.
  • the present invention provides a bionic digestive tract and a preparation method and application thereof.
  • the bionic digestive tract is based on a certain mass ratio between the substrate (one or more of silica gel, latex or hydrogel) and auxiliary materials (silicone oil and curing agent) (between the substrate, silicone oil and curing agent).
  • the mass ratio is 100: 0.5 ⁇ 10: 0.5 ⁇ 3.5). It is prepared after mixing, and its simulation performance is superior. It has strong consistency with human real digestive tract in terms of performance, structure and function, which can simulate food.
  • the real state of drugs, microorganisms, etc. in the digestive system has great application prospects in the research of food and drugs.
  • the invention provides a biomimetic material, the components of the biomimetic material include a base material and an auxiliary material; the base material includes one or more of silica gel, latex, or hydrogel; the auxiliary material includes silicone oil and curing Agent.
  • the mass ratio between the substrate, the silicone oil, and the curing agent is 100: (0.5 to 10): (0.5 to 3.5).
  • the substrate is silica gel.
  • the silica gel is transparent silica gel or translucent silica gel.
  • the curing agent comprises orthosilicate, vinyltriamine, DETA aminoethylpiperazine AE, m-phenylenediamine m-PDAMPD, diaminodiphenylmethane DDM or One or more of HT-972DEH-50.
  • the invention provides a bionic digestive tract, which is prepared by using a bionic material according to any one of claims 1-3; the digestive tract includes a stomach, a large intestine, an ileum, and a duodenum. , One or more of the jejunum.
  • the mass ratio between the base material, the silicone oil, and the curing agent is 100: (5-10): (1-3); or the digestive tract
  • the mass ratio between the substrate, the silicone oil and the curing agent is 100: (3-6): (1 to 3); or when the digestive tract is the ileum, the The mass ratio is 100: (2.5 to 3.5): (0.5 to 1.5); or when the digestive tract is duodenum, the mass ratio between the substrate, the silicone oil and the curing agent is 100: (0.5 to 1.5): (2.5 to 3.5); or when the digestive tract is a jejunum, the mass ratio between the substrate, the silicone oil, and the curing agent is 100: (1.5 to 2.5): (1.5 to 2.5).
  • the substrate is silica gel.
  • the silica gel is transparent silica gel or translucent silica gel.
  • the curing agent comprises orthosilicate, vinyltriamine, DETA aminoethylpiperazine AE, m-phenylenediamine m-PDAMPD, diaminodiphenylmethane DDM or One or more of HT-972DEH-50.
  • the invention provides a method for preparing a bionic stomach.
  • the method is to first prepare a gastric fundus, a gastric body and a gastric antrum mold having a real gastric fundus, a gastric body, and an internal physiological structure of the gastric antrum, and then bionic the stomach according to a certain thickness.
  • the raw material is smeared on the surface of the gastric fundus, gastric body, and antrum mold and left to stand, so that the bionic gastric raw material is solidified and formed, and the mold is removed to obtain a biomimetic stomach.
  • the gastric fundus, gastric body and gastric antrum molds are filled with plastic materials and filled with the accurate human gastric anatomical model of the medical digestive department.
  • the plastic material is cured and molded to obtain a gastric fundus, gastric body and gastric antrum mold having a real physiological structure of the gastric fundus, gastric body, and internal antrum of the stomach; the bionic gastric material is based on a certain mass ratio,
  • the auxiliary materials are mixed and put into a vacuum machine to evacuate the foam;
  • the substrate comprises one or more of silica gel, latex or hydrogel;
  • the auxiliary materials And a curing agent comprising a silicone oil.
  • the plastic material includes clay, paraffin, glass, or steel.
  • the clay is soft clay.
  • the preparation of the gastric fundus, gastric body, and gastric antrum molds with real physiological structures of the gastric fundus, gastric body, and internal antrum of the stomach is to put soft clay mud into and fill the medical digestive department respectively.
  • the accurate human stomach anatomy model in the medical digestive department is a real stomach 1: 1 hollow model.
  • the baking time is 15-30 minutes.
  • the mass ratio between the substrate, the silicone oil, and the curing agent is 100: (5 to 10): (1 to 3).
  • a mass ratio between the substrate, the silicone oil, and the curing agent is 100: 8: 2.
  • the substrate is silica gel.
  • the silica gel is transparent silica gel or translucent silica gel.
  • the curing agent comprises orthosilicate, vinyltriamine, DETA aminoethylpiperazine AE, m-phenylenediamine m-PDAMPD, diaminodiphenylmethane DDM or One or more of HT-972DEH-50.
  • the conditions for the vacuum evacuation and degassing are a vacuum negative pressure of -0.1 to 0.09 MPa, and a time of 5 to 10 minutes.
  • the conditions for the vacuum evacuation and degassing are a vacuum pressure of 0.09 MPa and a time of 7 minutes.
  • the thickness of the bionic gastric raw material applied on the surface of the stomach bottom, stomach body, and gastric antrum mold is 1 to 3 mm.
  • the thickness of the bionic gastric raw material applied on the surface of the gastric fundus, gastric body, and gastric antrum mold is 2 mm.
  • the standing time is 2 to 4 hours.
  • the standing time is 3h.
  • the invention provides a bionic stomach prepared by applying the above method.
  • the invention provides a method for preparing a bionic large intestine.
  • the method is to first prepare a large intestine mold having a true internal physiological structure of the large intestine, and then apply the bionic large intestine raw material on the surface of the large intestine mold according to a certain thickness and leave it to rest, so that the bionic large intestine.
  • the raw materials are solidified and formed, and the mold is removed to obtain a bionic large intestine.
  • a large intestine mold having a true internal physiological structure of the large intestine is prepared by placing and filling a plastic material into a large intestine of a precise human anatomy model of the medical digestive department, and then removing the medical digestive department.
  • the bionic large intestine material is obtained by mixing a base material and an auxiliary material for making a bionic large intestine according to a certain mass ratio It is obtained by putting into a vacuum machine to evacuate the bubble;
  • the substrate includes one or more of silica gel, latex, or hydrogel; and the auxiliary material includes silicone oil and a curing agent.
  • the plastic material includes clay, paraffin, glass, or steel.
  • the clay is soft clay.
  • the preparation of a large intestine mold having a true internal physiological structure of the large intestine is to put soft clay into and fill the large intestine of the accurate human anatomy model of the medical digestive department, and then remove the medical accurate
  • the large intestine of the human intestinal anatomical model is baked with soft clay to solidify it, and naturally cooled to prevent the mold from rapidly cooling to produce cracks, and a large intestine mold with a true internal physiological structure of the large intestine is obtained.
  • the accurate human intestinal anatomy model of the medical digestive department is a real 1: 1 hollow model of the intestine.
  • the large intestine mold has a diameter of 4 to 5 cm and a length of 20 to 30 cm.
  • the baking time is 15-30 minutes.
  • the mass ratio between the substrate, the silicone oil, and the curing agent is 100: (3 to 6): (1 to 3).
  • a mass ratio between the substrate, the silicone oil, and the curing agent is 100: 4: 2.
  • the substrate is silica gel.
  • the silica gel is transparent silica gel or translucent silica gel.
  • the curing agent comprises orthosilicate, vinyltriamine, DETA aminoethylpiperazine AE, m-phenylenediamine m-PDAMPD, diaminodiphenylmethane DDM or One or more of HT-972DEH-50.
  • the conditions for the vacuum evacuation and degassing are a vacuum negative pressure of -0.1 to 0.09 MPa, and a time of 5 to 10 minutes.
  • the conditions for the vacuum evacuation and degassing are a vacuum pressure of 0.09 MPa and a time of 7 minutes.
  • the thickness of the bionic large intestine raw material applied on the surface of the large intestine mold is 1 to 3 mm.
  • the thickness of the bionic large intestine raw material applied on the surface of the large intestine mold is 2 mm.
  • the standing time is 2 to 4 hours.
  • the standing time is 3h.
  • the invention provides a bionic large intestine prepared by applying the above method.
  • the invention provides a method for preparing a bionic ileum.
  • the method is to first prepare an ileal mold having a true internal physiological structure of the ileum and retaining needles, and then apply the bionic ileal raw material to the ileal mold and the human ileum according to a certain thickness.
  • the side where the anatomical model is in contact is left to stand, so that the raw material of the bionic ileum is solidified and formed.
  • the needle is pulled out and the mold is removed to obtain a hollow bionic ileum with small intestinal villi and a hollow body. Among them, a real ileal internal physiological structure is prepared and retained.
  • Needle-shaped ileum molds are filled with plastic materials and filled with accurate anatomical models of human ileum in medical digestive department, and then the human ileal anatomical models are removed, and each of the plastic materials corresponds to the small intestine villi on the human ileal anatomical model A small hole is pierced with a needle in the depression of the recess, and finally the needle is kept on the plastic material and the plastic material is cured and molded to obtain an ileal mold having a true internal ileum internal physiological structure and retaining the needle; Bionic ileal material is the basis for making bionic ileum according to a certain mass ratio. After mixing and put in a vacuum auxiliary machine vacuum bubble row obtained;
  • the method is to first prepare an ileal mold with a real internal ileal internal physiological structure and retain needles, and then apply the bionic ileal raw material on the side of the ileal mold that is in contact with the human ileal anatomical model according to a certain thickness and let it stand, The bionic ileum raw material is solidified and formed, and the needle is pulled out without taking off the mold to obtain a hollow bionic ileum with small intestinal villi, and then covering the side of the bionic ileum that is not in contact with the ileal mold.
  • the bionic ileal raw material is applied to the side of the separator that does not contact the bionic ileum with a certain thickness and left to stand, so that the bionic ileal raw material applied on the surface of the separator is solidified and formed, and the separator is removed and the mold is removed to obtain a ileal physiology.
  • Bionic ileum with a structure of villi and secretion of intestinal fluid among which, an ileum mold having a real internal ileum internal physiological structure and retaining needles is prepared, and a plastic material is put in and filled with a precise human ileal anatomical model in the medical digestive department, and then removed Human ileum anatomical model, then in each of the plastic materials with the human ileum On the cutaway model, the small intestine corresponding to the villi of the small intestine punctures small holes with needles. Finally, the needles are kept on the plastic material and the plastic material is cured and shaped to obtain a true ileal internal physiological structure and retain the needle shape.
  • the ileal mold of the object; the bionic ileal material is obtained by mixing the base material and the auxiliary material for making the bionic ileum according to a certain mass ratio and putting it in a vacuum machine to evacuate the foam;
  • the substrate includes one or more of silica gel, latex, or hydrogel; and the auxiliary material includes silicone oil and / or a curing agent.
  • the accurate human intestinal anatomy model of the medical digestive department is a real 1: 1 hollow model of the intestine.
  • the plastic material includes clay, paraffin, glass, or steel.
  • the plastic material includes clay, paraffin, glass, or steel.
  • the clay is soft clay.
  • the preparation of an ileal mold having a true internal ileal internal physiological structure and retaining needles is to place and fill a soft clay mud into a precise human ileal anatomical model in the medical digestive department, and then remove it.
  • Anatomical model of human ileum and then use a needle to poke out a small hole in each depression corresponding to the small intestine villi on the human ileal anatomical model.
  • the clay is baked to solidify and shape, and naturally cooled to prevent the mold from rapidly cooling to generate cracks, to obtain an ileal mold that has the true internal physiological structure of the ileum and retains needles.
  • the baking time is 15-30 minutes.
  • the diameter of the small hole is 0.2 to 1 mm.
  • the needles when a small hole is punctured in each of the depressions corresponding to the small intestine villi on the anatomical model of human ileum, the needles should penetrate the soft clay and make The end of the needle is at least 2 mm beyond the side where the soft clay touches the human ileal anatomical model.
  • the ileum mold has a diameter of 1.5 to 2.5 cm and a length of 20 to 30 cm.
  • the mass ratio between the substrate, the silicone oil, and the curing agent is 100: (2.5 to 3.5): (0.5 to 1.5).
  • the mass ratio between the substrate and the auxiliary material is 100: 3: 1.
  • the substrate is silica gel.
  • the silica gel is transparent silica gel or translucent silica gel.
  • the curing agent comprises orthosilicate, vinyltriamine, DETA aminoethylpiperazine AE, m-phenylenediamine m-PDAMPD, diaminodiphenylmethane DDM or One or more of HT-972DEH-50.
  • the conditions for the vacuum evacuation and degassing are a vacuum negative pressure of -0.1 to 0.09 MPa, and a time of 5 to 10 minutes.
  • the conditions for the vacuum evacuation and degassing are a vacuum pressure of 0.09 MPa and a time of 7 minutes.
  • the thickness of the bionic ileal raw material applied on the surface of the ileal mold is 2 to 3 mm.
  • the thickness of the bionic ileal raw material applied on the surface of the ileal mold is 2.5 mm.
  • the standing time is 2 to 4 hours.
  • the standing time is 3h.
  • the separator comprises an oily paper or a cling film.
  • the thickness of the bionic ileal raw material applied on the surface of the spacer is 2 to 3 mm.
  • the thickness of the bionic ileal raw material applied on the surface of the spacer is 2.5 mm.
  • the invention provides a bionic ileum prepared by applying the above method.
  • the invention provides a method for preparing a bionic duodenum.
  • the method is to first prepare an ileum mold having a true internal physiological structure of the duodenum and retaining needles, and then bionic the duodenum according to a certain thickness.
  • the intestinal raw material is smeared on the side where the duodenal mold is in contact with the human duodenal anatomical model and left to stand, so that the bionic duodenal raw material is solidified and formed.
  • the needle is pulled out and the mold is removed to obtain the intestinal villi.
  • a hollow bionic duodenum in which, a duodenum mold having a real internal physiological structure of the duodenum and retaining needles is prepared, and a plastic material is put in and filled with a precise human twelve in the medical digestive department.
  • Anatomy model of the duodenum then remove the anatomical model of the duodenum of the human body, and then use a needle to poke out a small hole in each depression of the plastic material corresponding to the small intestine villi on the human duodenal anatomical model.
  • the needles continue to be retained on the plastic material and the plastic material is cured and formed to obtain a duodenal mold having a true internal physiological structure of the duodenum and retaining the needles.
  • the biomimetic material is a duodenum according to a certain ratio of the mass production base bionic duodenum were mixed and placed in a vacuum auxiliary machine vacuum bubble row obtained;
  • the method is to first prepare an ileum mold with the actual internal physiological structure of the duodenum and retain needles, and then apply the bionic duodenal raw material to the duodenum mold and the human duodenum according to a certain thickness.
  • the intestinal anatomical model is in contact with the side and allowed to stand, so that the bionic duodenal raw material is solidified and formed.
  • the needles are pulled out without taking off the mold to obtain a hollow bionic duodenum with small intestinal villi and hollow.
  • the side of the duodenum that is not in contact with the duodenal mold is covered with a layer of spacer, and the bionic duodenal raw material is smeared on the side that does not contact the bionic duodenum according to a certain thickness.
  • the bionic duodenum raw material applied on the surface of the spacer is solidified and formed, and the spacer is removed and the mold is removed to obtain a bionic duodenum with duodenal physiological structure villi and secretion of intestinal fluid;
  • a duodenum mold having a true internal physiological structure of the duodenum and retaining needles is prepared by filling and filling a plastic material with accurate human duodenum anatomy in the medical digestive department Model, then remove the human duodenal anatomical model, and then poke small holes with needles in the depressions corresponding to the small intestinal villi on the human duodenal anatomical model, and finally pierce the needles
  • the bionic duodenal material is made according to a certain quality ratio
  • the base material and auxiliary materials of the bionic duodenum are mixed and put into a vacuum machine to
  • the substrate includes one or more of silica gel, latex, or hydrogel; and the auxiliary material includes silicone oil and / or a curing agent.
  • the accurate human intestinal anatomy model of the medical digestive department is a real 1: 1 hollow model of the intestine.
  • the plastic material includes clay, paraffin, glass, or steel.
  • the plastic material includes clay, paraffin, glass, or steel.
  • the clay is soft clay.
  • the preparation of a duodenum mold having a true internal physiological structure of the duodenum and retaining needles is to place soft clay into and fill the precise human body of the medical digestive department.
  • Anatomy model of duodenum then remove the anatomy model of human duodenum, and then poke small holes with needles in the depressions corresponding to the small intestinal villi on the duodenum anatomy model of human body.
  • the needles are kept on the soft clay, and the soft clay is baked to solidify and shape, and naturally cooled to prevent the mold from cooling quickly to produce cracks.
  • the actual physiological structure of the duodenum is retained and the needles are retained. Ileum mold.
  • the baking time is 15-30 minutes.
  • the diameter of the small hole is 0.2 to 1 mm.
  • the needles when a small hole is punctured in each of the depressions corresponding to the small intestinal villi on the duodenum anatomical model of the human body, the needles should penetrate the soft ceramic Mud and make the end of the needle at least 2mm beyond the side where the soft clay touches the human duodenal anatomical model.
  • the duodenum mold has a diameter of 3 to 4 cm and a length of 20 to 30 cm.
  • a mass ratio between the substrate, the silicone oil, and the curing agent is 100: (0.5 to 1.5): (2.5 to 3.5).
  • the mass ratio between the substrate and the auxiliary material is 100: 1: 3.
  • the substrate is silica gel.
  • the silica gel is transparent silica gel or translucent silica gel.
  • the curing agent comprises orthosilicate, vinyltriamine, DETA aminoethylpiperazine AE, m-phenylenediamine m-PDAMPD, diaminodiphenylmethane DDM or One or more of HT-972DEH-50.
  • the conditions for the vacuum evacuation and degassing are a vacuum negative pressure of -0.1 to 0.09 MPa, and a time of 5 to 10 minutes.
  • the conditions for the vacuum evacuation and degassing are a vacuum pressure of 0.09 MPa and a time of 7 minutes.
  • the thickness of the bionic duodenal raw material applied on the surface of the duodenal mold is 1 to 2 mm.
  • the thickness of the bionic duodenal raw material applied on the surface of the duodenal mold is 1.5 mm.
  • the standing time is 2 to 4 hours.
  • the standing time is 3h.
  • the separator comprises an oily paper or a cling film.
  • the thickness of the bionic duodenal raw material applied on the surface of the spacer is 1 to 5 mm.
  • the thickness of the bionic duodenal raw material applied on the surface of the spacer is 1.5 mm.
  • the invention provides a bionic duodenum prepared by applying the above method.
  • the invention provides a method for preparing a bionic jejunum.
  • the method is to first prepare a jejunum mold that has the actual physiological structure of the jejunum and retains needles, and then apply the bionic jejunum raw material to the jejunum mold and the human jejunum according to a certain thickness.
  • the contacting side of the anatomical model is left to stand to solidify the raw material of the bionic jejunum.
  • the needle is pulled out and the mold is removed to obtain a hollow bionic jejunum with small intestinal villi and hollow; among which, the real jejunum internal physiological structure is prepared and retained.
  • Needle-shaped jejunum mold is to put plastic material into and fill the precise human jejunum anatomical model of medical digestive department, then remove the human jejunum anatomical model, and then each of the plastic material corresponds to the small intestine villi on the human jejunum anatomical model A small hole is pierced with a needle in the depression of the hollow, and finally the needle is kept on the plastic material and the plastic material is cured and formed to obtain a jejunum mold having a real jejunum internal physiological structure and retaining the needle; The bionic jejunum material is based on a certain quality ratio. After mixing and put in a vacuum auxiliary machine vacuum bubble row obtained;
  • the method is to first prepare a jejunum mold that has the actual physiological structure of the jejunum and retains needles, and then apply the bionic jejunum raw material on the side of the jejunum mold that is in contact with the jejunum anatomical model of the human body according to a certain thickness and let it stand.
  • the bionic jejunum raw material is solidified and shaped, the needle is pulled out without taking off the mold, and a bionic jejunum with small intestinal villi and hollow is obtained, and then the side of the bionic jejunum that is not in contact with the jejunum mold is covered with a layer of spacers.
  • the bionic jejunum raw material is applied to the side where the spacer is not in contact with the bionic jejunum with a certain thickness and left to stand, so that the bionic jejunal raw material applied on the surface of the spacer is solidified and formed, the spacer is removed, and the mold is removed to obtain a jejunum physiology
  • a jejunum mold having a real physiological structure of the jejunum and retaining needles is prepared, and a plastic material is put in and filled with a precise human jejunum anatomical model of the medical digestive department, and then removed Human jejunum anatomical model, and then in each of the plastic materials with the human jejunum
  • the depressions corresponding to the small intestinal villi are used to poke small holes with needles.
  • the needles are kept on the plastic material and the plastic material is cured and shaped to obtain the true physiological structure of the jejunum and the needle shape.
  • the jejunum mold of the object; the bionic jejunum material is obtained by mixing the base material and the auxiliary material for making the bionic jejunum according to a certain mass ratio and putting it in a vacuum machine to evacuate the bubble;
  • the substrate includes one or more of silica gel, latex, or hydrogel; and the auxiliary material includes silicone oil and / or a curing agent.
  • the accurate human intestinal anatomy model of the medical digestive department is a real 1: 1 hollow model of the intestine.
  • the plastic material includes clay, paraffin, glass, or steel.
  • the plastic material includes clay, paraffin, glass, or steel.
  • the clay is soft clay.
  • the preparation of the jejunum mold having the real internal structure of the jejunum and retaining the needles is to place and fill the soft clay mud with a precise human jejunum anatomical model in the medical digestive department, and then remove it Anatomical model of human jejunum, and then use needles to poke small holes in each depression of soft terracotta clay that corresponds to the small intestine villi on the anatomical model of human jejunum. Finally, keep the needles on the soft clay and soften the clay The clay is baked to solidify and mold, and naturally cooled to prevent the mold from rapidly cooling to produce cracks, to obtain a jejunum mold that has the real physiological structure of the jejunum and retains needles.
  • the baking time is 15-30 minutes.
  • the diameter of the small hole is 0.2 to 1 mm.
  • the needles when a small hole is punctured in each of the depressions corresponding to the small intestine villi on the jejunum anatomical model of the human body, the needles should penetrate the soft clay and make The end of the needle is at least 2 mm beyond the side where the soft clay and the human jejunum anatomical model are in contact.
  • the jejunum mold has a diameter of 2 to 3 cm and a length of 20 to 30 cm.
  • the mass ratio between the substrate, the silicone oil, and the curing agent is 100: (1.5 to 2.5): (1.5 to 2.5).
  • the mass ratio between the substrate and the auxiliary material is 100: 2: 2.
  • the substrate is silica gel.
  • the silica gel is transparent silica gel or translucent silica gel.
  • the curing agent comprises orthosilicate, vinyltriamine, DETA aminoethylpiperazine AE, m-phenylenediamine m-PDAMPD, diaminodiphenylmethane DDM or One or more of HT-972DEH-50.
  • the conditions for the vacuum evacuation and degassing are a vacuum negative pressure of -0.1 to 0.09 MPa, and a time of 5 to 10 minutes.
  • the conditions for the vacuum evacuation and degassing are a vacuum pressure of 0.09 MPa and a time of 7 minutes.
  • the thickness of the bionic jejunum raw material applied on the surface of the jejunum mold is 1.5 to 2.5 mm.
  • the thickness of the bionic jejunum raw material applied on the surface of the jejunum mold is 2 mm.
  • the standing time is 2 to 4 hours.
  • the standing time is 3h.
  • the separator comprises an oily paper or a cling film.
  • the thickness of the bionic jejunum raw material applied on the surface of the spacer is 1.5 to 2.5 mm.
  • the thickness of the bionic jejunum raw material applied on the surface of the spacer is 2 mm.
  • the invention provides a bionic jejunum prepared by applying the above method.
  • the biomimetic digestive tract prepared by using the biomimetic material of the present invention has superior performance, has strong consistency in performance, structure, and function with the human real digestive tract, and can simulate food, medicine, microorganisms, etc.
  • the true state of the digestive system has great application prospects in the research of food and medicine.
  • the bionic digestive tract prepared by using the bionic material of the present invention can be transparent or translucent, and can realize the real-time and real-time observation of the internal digestive state of the digestive tract;
  • the bionic digestive tract prepared by using the bionic material of the present invention has the advantages of no stickiness, insolubility in water, non-reaction with acid and alkali, high and low temperature resistance, etc., and can well reproduce the digestive and absorbing environment in the digestive tract;
  • the simulation performance of the bionic stomach of the present invention is superior (Shore A hardness is 68 ⁇ 5, expansion rate is 36 ⁇ 5%, elasticity is 550 ⁇ 50%), and it has the real physiological structure of the real inner wall of the human stomach, which can realize the stomach
  • the function of the ground food has strong consistency in performance, structure, and function with the human real stomach; and the bionic stomach of the present invention separates the bionic gastric antrum and the gastric body, and separates the separated gastric antrum and By giving certain pressure to the gastric body, the function of "backspray" between the gastric body and gastric antrum can be realized;
  • the bionic large intestine of the present invention has superior simulation performance (Shore A hardness of 60 ⁇ 5, expansion rate of 31 ⁇ 5%, and elasticity of 460 ⁇ 50%). It has the morphology and physiological structure of a human large intestine, which can be real Simulates the digestive environment in the human large intestine. For example, the bionic large intestine has circular folds inside it, which can increase the surface area of the intestine, so that the bacterial flora in the large intestine can better digest and absorb food;
  • the simulation performance of the bionic ileum, duodenum and jejunum of the present invention is superior (Ileum: Shore A hardness 32 ⁇ 5, expansion rate 28 ⁇ 5%, elasticity 220 ⁇ 50%; duodenum: (Shore A hardness is 40 ⁇ 5, expansion rate is 22 ⁇ 5%, elasticity is 250 ⁇ 50%; jejunum: Shore A hardness is 36 ⁇ 5, expansion ratio is 25 ⁇ 5%, elasticity is 250 ⁇ 50%)
  • the morphology and physiological structure of the human intestinal tract can realistically simulate the digestive environment in the human intestinal tract; the bionic ileum, duodenum and jejunum of the present invention have circular folds inside, which can increase the surface area of the intestine, which can in turn For the microbial flora in the ileum to better digest and absorb food; the bionic ileum, duodenum, and jejunum of the present invention have small intestinal villi and the small intestinal villi can have a double-layered hollow structure, and the intestinal fluid
  • Figure 1 Photograph of gastric fundus of the present invention
  • FIG. 1 Photo of the stomach body of the present invention
  • FIG. 3 Photo of gastric antrum of the present invention
  • FIG. 4 Overall picture of the stomach of the present invention.
  • Figure 5 Frontal photos of bionic ileum, duodenum and jejunum of the present invention
  • Figure 6 Photographs of the reverse side of the bionic ileum, duodenum and jejunum of the present invention
  • Figure 7 Photographs of villi of the small intestine of the bionic ileum, duodenum and jejunum of the present invention.
  • S is the area of the stomach
  • r 1 is the radius of the gastric fundus
  • h 1 is the height of the gastric fundus
  • n 1 is the number of the gastric wall
  • r 2 is the radius of the gastric body
  • h 2 is the height of the gastric body
  • n 2 is the number of the gastric wall
  • R 3 is the radius of the gastric antrum
  • h 3 is the height of the gastric antrum
  • n 3 is the number of gastric antrum.
  • S is intestinal area
  • r 1 is intestinal radius
  • h 1 is intestinal height
  • n is intestinal wall number
  • r 2 is intestinal wall radius
  • h 2 is intestinal wall height.
  • the bionic stomach is fixed to the gastric body visualization bionic reactor (see the invention patent for publication number CN108088966A for gastric body visualization bionic reactor), 100 ml of milk is added, and the water flow solenoid valve of the reactor is opened by operating the reactor to give pressure to the bionic gastric antrum To see if the "backspray function" of milk in the gastric antrum can be sprayed back to the stomach body.
  • the transparency is good; if the outline of the food can be seen, the transparency is moderate; if the object of the food cannot be seen, the transparency is poor.
  • the measurement was performed with a Shore hardness tester, and the pressure needle of the hardness tester was pressed against the surface of the stomach, and the depth of the pressure needle pressed into the surface of the stomach was measured.
  • Pe is the expansion rate
  • W is the total equilibrium load
  • A is the area of the silica gel
  • m is the leverage ratio of the pressurized equipment.
  • a tensile test was performed on the silicone rubber on a tensile tester, and the axial and lateral elongation of the silicone rubber was measured until the silicone rubber broke.
  • C is the elastic modulus
  • D is the elongation amount
  • d is the initial length of the silica gel.
  • the obtained bionic duodenum was fixed in the intestinal visualization bionic reactor through the flange interface of the pipeline (see the intestinal visualization bionic reactor for the invention patent CN108318625A), and 100 ml of pancreatic juice was added to the silicone bionic duodenum During operation, the reactor was run for 10 minutes, and the volume of secreted pancreatic juice was observed.
  • Stomach body mold roasting and molding Put the stomach body mold into the oven and bake for 15 minutes, solidify the stomach body mold, cool naturally, and obtain a bionic stomach body mold;
  • Stomach antrum mold baking molding Put the antrum mold into the oven and bake for 15 minutes, solidify the antrum mold, cool naturally, and obtain a bionic antrum mold;
  • silica gel Put transparent silica gel, silicone oil and curing agent orthosilicate according to 100: 8: 2 in a beaker, stir thoroughly and mix well;
  • the three uniformly applied molds are allowed to stand for 2 hours to completely solidify and mold. After removing the molds, they are subjected to a certain trimming treatment to obtain a silicone bionic gastric fundus, a silicone bionic gastric body and a silicone bionic gastric antrum.
  • the mold baking time in steps (3), (5), and (7) was changed to 20 minutes; the curing agent in step (8) was changed to diaminodiphenylmethane DDM At the same time, change the mass ratio of transparent silicone, silicone oil and curing agent to 100: 7: 1.5; change the defoaming time in step (9) to 10 minutes; change the smear thickness in step (10) to 2mm; The standing time in step (11) becomes 4 hours.
  • the mold baking time in steps (3), (5), and (7) was changed to 30 minutes; the curing agent in step (8) was changed to vinyltriamine, and at the same time
  • the mass ratio of the transparent silica gel, the silicone oil, and the curing agent becomes 100: 9: 3; the coating thickness in step (10) is changed to 3 mm; and the standing time in step (11) is changed to 1 hour.
  • Comparative Example 1.1 Preparation of a bionic stomach (no internal biological structure of the stomach)
  • the step (2) is changed to: making the kneaded soft clay into a shape of the gastric fundus with a smooth surface to obtain a gastric fundus mold; and the step (4) is changed to: kneading the softened clay
  • the clay body is made into a smooth stomach shape to obtain a stomach body mold.
  • Step (6) is changed to: the kneaded soft clay is made into a smooth gastric antrum shape to obtain a gastric antrum mold.
  • Step (3), (5), (7) The mold baking time is changed to 30 minutes; the mass ratio of the transparent silicone, silicone oil and curing agent in step (8) is changed to 100: 5: 2; The application thickness becomes 2mm.
  • the steps (2) to (7) are changed to: first make the kneaded soft clay into a smooth stomach shape to obtain a stomach bottom mold, and then place the stomach mold in the oven for baking In 30 minutes, the stomach mold was solidified and formed to cool naturally to obtain a stomach mold; the mass ratio of the transparent silicone, the silicone oil and the curing agent in step (8) was changed to 100: 6: 1; and the thickness of the application in step (10) was changed. It becomes 2mm.
  • the mold baking time in steps (3), (5), and (7) was changed to 30 minutes; the mass ratio of transparent silicone, silicone oil, and curing agent in step (8) was changed to 100: 10: 3; omit step (9); change the coating thickness in step (10) to 3 mm; change the standing time in step (11) to 1 hour.
  • Comparative Example 1.4 Preparation of bionic stomach (increased thickness of smeared silica gel)
  • the mold baking time in steps (3), (5), and (7) was changed to 30 minutes; the mass ratio of transparent silicone, silicone oil, and curing agent in step (8) was changed to 100: 8: 2; omit step (9); change the smear thickness in step (10) to 6mm; change the standing time in step (11) to 1 hour.
  • the mold baking time in steps (3), (5), and (7) was changed to 30 minutes; the silicone oil in step (8) was omitted, and the transparent silicone and curing agent The mass ratio becomes 100: 3; the smear thickness in step (10) is 2 mm; and the standing time in step (11) is 1 hour.
  • the mold baking time in steps (3), (5), and (7) was changed to 30 minutes; the silicone oil in step (8) was replaced with glycerin; and the step (10) The thickness of the coating was changed to 2 mm; the standing time in step (11) was changed to 1 hour.
  • the human stomach anatomy model, the bionic stomach prepared in Examples 1.1-1.3, the bionic stomach prepared in Comparative Examples 1.1-1.6, and similar foreign products were performed in the stomach.
  • the area, food grinding function, back-jet function, transparency, hardness, expansion rate and elasticity are tested.
  • the test results are shown in Table 1.
  • the index comparison between the bionic stomach of the present invention and the real stomach is relatively close, and the index is superior to similar foreign products. Therefore, the bionic stomach of the present invention can replace the real stomach to predict a living test, completely or partially. In vivo tests can achieve the purpose of reducing cost and time, improving repeatability and accuracy, and there is no theoretical limit.
  • silica gel Put transparent silica gel, silicone oil and curing agent ethyl orthosilicate according to 100: 5: 2 in a beaker, stir well and mix well;
  • the mold diameter in step (2) was changed to 4.5 cm; the curing agent in step (4) was replaced with vinyl triamine, and the mass ratio of transparent silicone, silicone oil and curing agent was simultaneously Becomes 100: 4: 1; the thickness of the application in step (6) is changed to 2 mm; and the standing time in step (7) is changed to 4 hours.
  • the mold diameter in step (2) was changed to 5 cm; the curing agent in step (4) was replaced with diaminodiphenylmethane DDM, and the transparent silicone, silicone oil and curing agent were The mass ratio becomes 100: 6: 3; the smear thickness in step (6) becomes 3 mm.
  • step (2) is changed to: knead the soft clay clay into a long cylinder with a smooth surface, the mold diameter is 4cm, and the length is 30cm; the baking conditions in step (3) are changed Bake at 130 ° C for 30 minutes; change the mass ratio of transparent silica gel, silicone oil, and curing agent in step (4) to 100: 5: 3; change the coating thickness in step (6) to 2mm; change step (7) The standing time in the middle becomes 1 hour.
  • step (2) Based on Example 2.1, the mold diameter in step (2) was changed to 4.5 cm; the baking conditions in step (3) were changed to 130 ° C for 30 minutes; and the transparent silica gel in step (4), The mass ratio of the silicone oil and the curing agent becomes 100: 6: 2; step (5) is omitted; and the application thickness in step (6) is changed to 2 mm.
  • step (2) change the diameter of the mold in step (2) to 5cm; change the baking conditions in step (3) to 130 ° C for 30 minutes; replace the curing agent in step (4) Is a vinyl triamine, and the mass ratio of the transparent silica gel, the silicone oil, and the curing agent is changed to 100: 3: 3; and the coating thickness in step (6) is changed to 8 mm.
  • the diameter of the mold in step (2) was changed to 5 cm; the baking conditions in step (3) were changed to 150 ° C for 15 minutes; and the silicone oil in step (4) was omitted.
  • the mass ratio of the transparent silicone curing agent was changed to 100: 3; the thickness of the coating in step (6) was changed to 2 mm.
  • Example 2.1 Based on Example 2.1, change the diameter of the mold in step (2) to 5cm; change the baking conditions in step (3) to 150 ° C for 15 minutes; replace the silicone oil in step (4) with Glycerin; change the smear thickness in step (6) to 2 mm.
  • the index comparison of the bionic large intestine of the present invention is close to that of the real large intestine. Compared with similar foreign products, the index is better. Therefore, the bionic large intestine of the present invention can replace the real large intestine to predict living tests, completely or partially. In vivo tests can achieve the purpose of reducing cost and time, improving repeatability and accuracy, and there is no theoretical limit.
  • Ileum mold compression Put the kneaded soft clay into the accurate human ileum anatomical model in the medical digestive department, squeeze it hard, remove the human ileal anatomical model, and get the soft terra clay ileum with the real internal physiological structure of the ileum. Mold, mold diameter 1.5cm, length 25cm;
  • silica gel Put transparent silica gel, silicone oil and ethyl orthosilicate according to 100: 3: 1 in a beaker, stir thoroughly and mix well
  • the diameter of the mold in step (2) was changed to 2 cm; the diameter of the needle in step (3) was changed to 0.3 mm, and the diameter of the small hole was changed to 0.5 mm;
  • the baking conditions were changed to 150 ° C for 20 minutes; the curing agent in step (5) was changed to vinyltriamine, and the mass ratio of transparent silica gel, silicone oil and curing agent was changed to 100: 3: 1.5;
  • the coating thickness in (7) is 2.5 mm; the standing time in step (8) is 4 hours; and the standing time in step (10) is 1 hour.
  • Example 3.1 change the diameter of the mold in step (2) to 2.5 cm and length to 30 cm; change the diameter of the needle in step (3) to 0.1 mm, and the diameter of the small hole to 0.2 mm; Change the baking conditions in step (4) to 130 ° C for 30 minutes; change the curing agent in step (5) to diaminodiphenylmethane DDM, and change the mass ratio of transparent silica gel, silicone oil, and curing agent It is 100: 2.5: 1; the smear thickness in step (7) is changed to 3 mm; the standing time in step (8) is changed to 1 hour; and the standing time in step (10) is changed to 1 hour.
  • Example 3.1 Based on Example 3.1, change the diameter of the mold in step (2) to 2.5cm and length to 30cm; omit step (3); change the baking conditions in step (4) to 130 ° C for 30 minutes ; Change the mass ratio of transparent silica gel, silicone oil and curing agent in step (5) to 100: 3.5: 0.5; change the thickness of the application in step (7) to 2.5mm; change step (8) to: uniformly apply The ileum mold was left for 1 hour to completely solidify and mold; steps (9)-(11) were omitted.
  • step (2) change the diameter of the mold in step (2) to 2 cm and length to 30 cm; change the diameter of the needle in step (3) to 0.2 mm and the diameter of the small hole to 0.5 mm;
  • the baking conditions in step (4) were changed to 140 ° C for 20 minutes; the mass ratio of transparent silicone, silicone oil and curing agent in step (5) was changed to 100: 3: 0.5; step (6) was omitted; and step ( The coating thickness in 7) becomes 2.5 mm.
  • Example 3.1 Based on Example 3.1, change the diameter of the mold in step (2) to 2 cm and length to 30 cm; change the diameter of the needle in step (3) to 0.4 mm and the diameter of the small hole to 0.6 mm;
  • the baking condition in step (4) was changed to 130 ° C for 30 minutes; the mass ratio of transparent silicone, silicone oil and curing agent in step (5) was changed to 100: 2.5: 1.5; and the thickness of the coating in step (7) was changed. It becomes 6mm.
  • Example 3.1 Based on Example 3.1, change the diameter of the mold in step (2) to 2 cm and length to 30 cm; change the diameter of the needle in step (3) to 0.4 mm and the diameter of the small hole to 0.6 mm; The baking conditions in step (4) were changed to 130 ° C for 30 minutes; the silicone oil in step (5) was omitted.
  • Example 3.1 change the diameter of the mold in step (2) to 2 cm and length to 30 cm; change the diameter of the needle in step (3) to 0.4 mm and the diameter of the small hole to 0.6 mm;
  • the baking conditions in step (4) were changed to 130 ° C for 30 minutes; the silicone oil in step (5) was replaced with glycerin.
  • the index comparison between the bionic ileum of the present invention and the real ileum is relatively close, and the index is superior to similar foreign products. Therefore, the bionic ileum of the present invention can replace the real ileum to predict living tests, completely or partially. In vivo tests can achieve the purpose of reducing cost and time, improving repeatability and accuracy, and there is no theoretical limit.
  • Duodenum mold compression Put the kneaded soft clay into a precise human duodenum anatomical model in the medical digestive department, squeeze it hard, and remove the human duodenal anatomical model to get a real Soft clay mud duodenum mold with internal physiological structure of duodenum, mold diameter 3cm, length 25cm;
  • Duodenal mold roasting and molding Put the duodenal mold in the oven at 140 ° C for 15 minutes, solidify the duodenal mold, cool naturally, and obtain a bionic duodenal mold;
  • silica gel Put transparent silica gel, silicone oil and curing agent ethyl orthosilicate according to 100: 1: 3 in a beaker, stir thoroughly and mix well;
  • duodenum mold evenly applied is left for 2 hours to completely solidify, and then the needle outside the mold is pulled out to obtain a hollow duodenum silicone model with small intestinal villi;
  • the mold diameter in step (2) was changed to 3.5 cm; the diameter of the needle in step (3) was changed to 0.3 mm, and the diameter of the small hole was changed to 0.5 mm; and step (4)
  • the baking conditions were changed to 150 ° C for 20 minutes; the curing agent in step (5) was changed to vinyltriamine, and the mass ratio of transparent silica gel, silicone oil and curing agent was changed to 100: 1.5: 3;
  • the thickness of the application in step (7) is 1.5 mm; the standing time in step (8) is 4 hours; and the standing time in step (10) is 1 hour.
  • Example 4.1 change the diameter of the mold in step (2) to 4 cm and length to 30 cm; change the diameter of the needle in step (3) to 0.1 mm, and the diameter of the small hole to 0.2 mm;
  • the baking conditions in step (4) were changed to 130 ° C for 30 minutes;
  • the curing agent in step (5) was changed to diaminodiphenylmethane DDM, and the mass ratio of transparent silicone, silicone oil and curing agent was changed to 100: 1: 2.5; change the smear thickness in step (7) to 2mm; change the rest time in step (8) to 1 hour; change the rest time in step (10) to 1 hour.
  • step (2) Based on Example 4.1, the mold length in step (2) was changed to 30 cm; step (3) was omitted; the baking conditions in step (4) were changed to 130 ° C for 30 minutes; and step (5)
  • the mass ratio of medium transparent silicone, silicone oil and curing agent becomes 100: 1: 3; the thickness of the application in step (7) becomes 1.5mm; and the step (8) becomes: the ileal mold applied evenly is allowed to stand 1 Hours, it is completely solidified; steps (9)-(11) are omitted.
  • Example 4.1 change the diameter of the mold in step (2) to 3.5 cm and length to 30 cm; change the diameter of the needle in step (3) to 0.2 mm, and the diameter of the small hole to 0.5 mm; Change the baking conditions in step (4) to 140 ° C for 20 minutes; change the mass ratio of transparent silica gel, silicone oil to curing agent in step (5) to 100: 0.5: 2.5; omit step (6); change step The coating thickness in (7) becomes 1.5 mm.
  • Example 4.1 Based on Example 4.1, change the diameter of the mold in step (2) to 4 cm and length to 30 cm; change the diameter of the needle in step (3) to 0.4 mm and the diameter of the small hole to 0.6 mm;
  • the baking condition in step (4) was changed to 130 ° C for 30 minutes; the mass ratio of transparent silicone, silicone oil and curing agent in step (5) was changed to 100: 1.5: 3.5; and the coating thickness in step (7) was changed. It becomes 6mm.
  • Example 4.1 Based on Example 4.1, change the diameter of the mold in step (2) to 4 cm and length to 30 cm; change the diameter of the needle in step (3) to 0.4 mm and the diameter of the small hole to 0.6 mm; The baking conditions in step (4) were changed to 130 ° C for 30 minutes; the silicone oil in step (5) was omitted.
  • Example 4.1 Based on Example 4.1, change the diameter of the mold in step (2) to 4 cm and length to 30 cm; change the diameter of the needle in step (3) to 0.4 mm and the diameter of the small hole to 0.6 mm;
  • the baking conditions in step (4) were changed to 130 ° C for 30 minutes; the silicone oil in step (5) was replaced with glycerin.
  • the index of the bionic duodenum of the present invention is close to that of the real duodenum. Compared with similar foreign products, the index is better. Therefore, the bionic duodenum of the present invention can replace the real duodenum.
  • the intestine is used to predict a living test, completely or partially replacing a living test, to achieve the purpose of reducing costs and time, improving repeatability and accuracy, and there is no theoretical limit.
  • Jejunum mold compression Put the kneaded soft clay into the precise human jejunum anatomical model of the medical digestive department, and squeeze it vigorously to remove the human jejunum anatomical model to obtain the soft ceramic mud jejunum with the internal physiological structure of the real jejunum Mold, mold diameter 2cm, length 25cm;
  • silica gel Put transparent silica gel, silicone oil and curing agent ethyl orthosilicate according to 100: 2: 2 in a beaker, stir well and mix well;
  • step 5.1 change the diameter of the mold in step (2) to 3 cm and length to 30 cm; change the diameter of the needle in step (3) to 0.1 mm and the diameter of the small hole to 0.2 mm;
  • the baking conditions in step (4) were changed to 130 ° C for 30 minutes;
  • the curing agent in step (5) was changed to diaminodiphenylmethane DDM, and the mass ratio of transparent silicone, silicone oil and curing agent was changed to 100: 2: 2.5; change the smear thickness in step (7) to 2.5 mm; change the rest time in step (8) to 1 hour; change the rest time in step (10) to 1 hour.
  • step (2) change the diameter of the mold in step (2) to 2.5cm and length to 30cm; omit step (3); change the baking conditions in step (4) to 130 ° C for 30 minutes ; Change the mass ratio of transparent silicone, silicone oil and curing agent in step (5) to 100: 1.5: 2.5; change the thickness of the application in step (7) to 2mm; change step (8) to: uniformly apply The ileum mold was allowed to stand for 1 hour to completely solidify and mold; steps (9)-(11) were omitted.
  • Example 5.1 change the diameter of the mold in step (2) to 2.5 cm and length to 30 cm; change the diameter of the needle in step (3) to 0.2 mm, and the diameter of the small hole to 0.5 mm; Change the baking conditions in step (4) to 140 ° C for 20 minutes; change the mass ratio of transparent silicone, silicone oil and curing agent in step (5) to 100: 2.5: 1.5; omit step (6); change step The coating thickness in (7) becomes 2 mm.
  • step 5.1 change the diameter of the mold in step (2) to 2.5 cm and length to 30 cm; change the diameter of the needle in step (3) to 0.4 mm, and the diameter of the small hole to 0.6 mm;
  • the baking conditions in step (4) were changed to 130 ° C for 30 minutes; the silicone oil in step (5) was replaced with glycerin.
  • the bionic jejunum of the present invention can replace the real jejunum to predict a living test, completely or partially Instead of living test, the purpose of reducing cost and time, improving repeatability and accuracy is achieved, and there is no theoretical limit.

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Abstract

一种仿生消化道及其制备方法和应用，属于仿生技术领域以及生物技术领域。该仿生消化道是通过将基材--硅胶、乳胶或水凝胶中的一种或多种和辅材--硅油以及固化剂按照一定的质量比---基材、硅油以及固化剂之间的质量比为100:0.5～10:0.5～3.5，混合后制备得到的，其仿真性能优越，可模拟食品、药品、微生物等在消化系统中的真实状态，在食品、药品的研究过程中具有应用前景。

Description

一种仿生消化道及其制备方法和应用 技术领域
本发明涉及一种仿生消化道及其制备方法和应用，属于仿生技术领域以及生物技术领域。
背景技术
在食品、药品的研究过程中，客观精确地评定食物、药品在人体内的消化过程对于确定食物组分、药品组分以及它们对人体消化道的作用至关重要。
人消化道体外模拟装置(如SHIME、IViDiS、TIM、DGM、HGS等)是对人的消化系统及其消化环境、消化道内的流体动态行为进行仿生模拟的装置，可模拟不同样品在体外模型中的消化过程以及这些样品对肠道微生物的影响，从而为新型功能性食品的研发提供大量有价值的数据，若将其作为“前测试”来预测活体试验，完全代替或部分代替活体试验，可达到降低成本和时间、提高重复性和准确性的目的，且没有理论限制。
因此，人消化道体外模拟装置在对食品、药品，甚至微生物等的研究中越发关键，为食品科学、人类营养学的研究提供了巨大的方便，是小鼠实验或人类志愿者实验所不能比拟的。
而模拟消化道(主要包括胃、小肠、大肠)作为人消化道体外模拟装置的主体，其对人真实消化道的仿真程度在整个人消化道体外模拟装置的仿真性能中至关重要。
目前，人们通常使用硅胶、乳胶等材料来制作模拟消化道模型，可很好的重现消化道内的消化环境，如无粘性、不溶于水、不与酸碱起反应、耐高低温等。
但现有的这些用硅胶、乳胶制作的消化道模型的内部生理结构均为平滑的，不具有磨碎食物的功能，仅仅可真实的模拟一些不需要磨碎的流食(饮料、牛奶等)在胃内的消化状态；而对于固体(米饭、水果、肉等)或半固体(粥、汤等)食物，它们仅仅能体现混合食物的功能，不能够真实的体现胃肠道磨碎、消化食物的功能。
并且，这些消化道模型常常被简单的制作为整体结构，例如，用硅胶或乳胶一次性成型成整胃，这些整胃不可以模拟胃窦和胃体之间的“回喷流”功能，导致实验的测定结果不准确。
同时，这些由硅胶、乳胶制作的消化道模型在仿真性能，例如硬度、膨胀率、弹性方面实际上并不尽如人意，与人真实的消化道依旧存在一定的差距。
因此，急需对仿生消化道进行创新升级以提升其仿真性能、提升其模拟真实人体消化道的消化环境(无粘性、不溶于水、不与酸碱起反应、耐高低温)以及消化道各部位的功能的真实性。
发明内容
为解决上述问题，本发明提供了一种仿生消化道及其制备方法和应用。此仿生消化道是通过将基材(硅胶、乳胶或水凝胶中的一种或多种)和辅材(硅油以及固化剂)按照一定的质量比(基材、硅油以及固化剂之间的质量比为100:0.5～10:0.5～3.5)混合后制备得到的，其仿真性能优越，与人真实消化道的在性能上、结构上以及功能上均具有极强的一致性，可模拟食品、药品、微生物等在消化系统中的真实状态，在食品、药品的研究过程中具有极大的应用前景。
本发明的技术方案如下：
本发明提供了一种仿生材料，所述仿生材料的成分包含基材和辅材；所述基材包含硅胶、乳胶或水凝胶中的一种或多种；所述辅材包含硅油以及固化剂。
在本发明的一种实施方式中，所述基材、硅油以及固化剂之间的质量比为100:(0.5～10):(0.5～3.5)。
在本发明的一种实施方式中，所述基材为硅胶。
在本发明的一种实施方式中，所述硅胶为透明硅胶或半透明硅胶。
在本发明的一种实施方式中，所述固化剂包含正硅酸乙酯、乙烯基三胺、DETA氨乙基哌嗪AE、间苯二胺m-PDAMPD、二氨基二苯基甲烷DDM或HT-972DEH-50中的一种或多种。
本发明提供了一种仿生消化道，所述仿生消化道是使用权利要求1-3任一所述的一种仿生材料制备得到的；所述消化道包含胃、大肠、回肠、十二指肠、空肠中的一种或多种。
在本发明的一种实施方式中，所述消化道为胃时，基材、硅油以及固化剂之间的质量比为100:(5～10):(1～3)；或所述消化道为大肠时，基材、硅油以及固化剂之间的质量比为100:(3～6):(1～3)；或所述消化道为回肠时，基材、硅油以及固化剂之间的质量比为100:(2.5～3.5):(0.5～1.5)；或所述消化道为十二指肠时，基材、硅油以及固化剂之间的质量比为100:(0.5～1.5):(2.5～3.5)；或所述消化道为空肠时，基材、硅油以及固化剂之间的质量比为100:(1.5～2.5):(1.5～2.5)。
在本发明的一种实施方式中，所述基材为硅胶。
在本发明的一种实施方式中，所述硅胶为透明硅胶或半透明硅胶。
在本发明的一种实施方式中，所述固化剂包含正硅酸乙酯、乙烯基三胺、DETA氨乙基哌嗪AE、间苯二胺m-PDAMPD、二氨基二苯基甲烷DDM或HT-972DEH-50中的一种或多种。
本发明提供了一种仿生胃的制备方法，所述方法为先制备具有真实胃底、胃体以及胃窦内部生理结构的胃底、胃体以及胃窦模具，然后按照一定的厚度将仿生胃原材料涂抹在胃底、胃体以及胃窦模具的表面并静置，使仿生胃原材料凝固成型，脱去模具，得到仿生胃；其中，制备具有真实胃底、胃体以及胃窦内部生理结构的胃底、胃体以及胃窦模具，是将可塑性材料分别放入并充满医学消化科精准人体胃解剖模型的胃底、胃体以及胃窦，然后取下医学消化科精准人体胃解剖模型并对可塑性材料进行固化成型，得到具有真实胃底、胃体以及胃窦内部生理结构的胃底、胃体以及胃窦模具；所述仿生胃材料是按照一定的质量比将制作仿生胃的基材和辅材进行混合后放入真空机中抽真空排泡得到的；所述基材包含硅胶、乳胶或水凝胶中的一种或多种；所述辅材包含硅油以及固化剂。
在本发明的一种实施方式中，所述可塑性材料包含陶土、石蜡、玻璃或钢铁。
在本发明的一种实施方式中，所述陶土为软陶泥。
在本发明的一种实施方式中，所述制备具有真实胃底、胃体以及胃窦内部生理结构的胃底、胃体以及胃窦模具，是将软陶泥分别放入并充满医学消化科精准人体胃解剖模型的胃底、胃体以及胃窦，然后取下医学消化科精准人体胃解剖模型并对软陶泥进行烤制使其固化成型，自然冷却以防止模具快速冷却产生裂缝，得到具有真实胃底、胃体以及胃窦内部生理结构的胃底、胃体以及胃窦模具。
在本发明的一种实施方式中，所述医学消化科精准人体胃解剖模型为真实胃1:1中空模型。
在本发明的一种实施方式中，所述烤制的时间为15～30min。
在本发明的一种实施方式中，所述基材、硅油以及固化剂之间的质量比为100:(5～10):(1～3)。
在本发明的一种实施方式中，所述基材、硅油以及固化剂之间的质量比为100:8:2。
在本发明的一种实施方式中，所述基材为硅胶。
在本发明的一种实施方式中，所述硅胶为透明硅胶或半透明硅胶。
在本发明的一种实施方式中，所述固化剂包含正硅酸乙酯、乙烯基三胺、DETA氨乙基哌嗪AE、间苯二胺m-PDAMPD、二氨基二苯基甲烷DDM或HT-972DEH-50中的一种或多种。
在本发明的一种实施方式中，所述抽真空排泡的条件为真空机负压-0.1～0.09MPa、时间5～10min。
在本发明的一种实施方式中，所述抽真空排泡的条件为真空机负压0.09MPa、时间7min。
在本发明的一种实施方式中，所述仿生胃原材料涂抹在胃底、胃体以及胃窦模具表面的厚度为1～3mm。
在本发明的一种实施方式中，所述仿生胃原材料涂抹在胃底、胃体以及胃窦模具表面的厚度为2mm。
在本发明的一种实施方式中，所述静置的时间为2～4h。
在本发明的一种实施方式中，所述静置的时间为3h。
本发明提供了应用上述方法制备得到的仿生胃。
本发明提供了一种仿生大肠的制备方法，所述方法为先制备具有真实大肠内部生理结构的大肠模具，然后按照一定的厚度将仿生大肠原材料涂抹在大肠模具的表面并静置，使仿生大肠原材料凝固成型，脱去模具，得到仿生大肠；其中，制备具有真实大肠内部生理结构的大肠模具，是将可塑性材料放入并充满医学消化科精准人体肠道解剖模型大肠，然后取下医学消化科精准人体肠道解剖模型大肠并对可塑性材料进行固化成型，得到具有真实大肠内部生理结构的大肠模具；所述仿生大肠材料是按照一定的质量比将制作仿生大肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的；所述基材包含硅胶、乳胶或水凝胶中的一种或多种；所述辅材包含硅油以及固化剂。
在本发明的一种实施方式中，所述可塑性材料包含陶土、石蜡、玻璃或钢铁。
在本发明的一种实施方式中，所述陶土为软陶泥。
在本发明的一种实施方式中，所述制备具有真实大肠内部生理结构的大肠模具，是将软陶泥放入并充满医学消化科精准人体肠道解剖模型大肠，然后取下医学消化科精准人体肠道解剖模型大肠并对软陶泥进行烤制使其固化成型，自然冷却以防止模具快速冷却产生裂缝，得到具有真实大肠内部生理结构的大肠模具。
在本发明的一种实施方式中，所述医学消化科精准人体肠道解剖模型为真实肠道1:1中空模型。
在本发明的一种实施方式中，所述大肠模具的直径为4～5cm，长度为20～30cm。
在本发明的一种实施方式中，所述烤制的时间为15～30min。
在本发明的一种实施方式中，所述基材、硅油以及固化剂之间的质量比为100:(3～6):(1～3)。
在本发明的一种实施方式中，所述基材、硅油以及固化剂之间的质量比为100:4:2。
在本发明的一种实施方式中，所述基材为硅胶。
在本发明的一种实施方式中，所述硅胶为透明硅胶或半透明硅胶。
在本发明的一种实施方式中，所述固化剂包含正硅酸乙酯、乙烯基三胺、DETA氨乙基哌嗪AE、间苯二胺m-PDAMPD、二氨基二苯基甲烷DDM或HT-972DEH-50中的一种或多种。
在本发明的一种实施方式中，所述抽真空排泡的条件为真空机负压-0.1～0.09MPa、时间5～10min。
在本发明的一种实施方式中，所述抽真空排泡的条件为真空机负压0.09MPa、时间7min。
在本发明的一种实施方式中，所述仿生大肠原材料涂抹在大肠模具表面的厚度为1～3mm。
在本发明的一种实施方式中，所述仿生大肠原材料涂抹在大肠模具表面的厚度为2mm。
在本发明的一种实施方式中，所述静置的时间为2～4h。
在本发明的一种实施方式中，所述静置的时间为3h。
本发明提供了应用上述方法制备得到的仿生大肠。
本发明提供了一种仿生回肠的制备方法，所述方法为先制备具有真实回肠内部生理结构且保留有针状物的回肠模具，然后按照一定的厚度将仿生回肠原材料涂抹在回肠模具与人体回肠解剖模型相接触的一面上并静置，使仿生回肠原材料凝固成型，拔出针状物且脱去模具，得到具有小肠绒毛且为中空的仿生回肠；其中，制备具有真实回肠内部生理结构且保留有针状物的回肠模具，是将可塑性材料放入并充满医学消化科精准人体回肠解剖模型，然后取下人体回肠解剖模型，再在可塑性材料的每一个与人体回肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞，最后将针状物继续保留在可塑性材料上并对可塑性材料进行固化成型，得到具有真实回肠内部生理结构且保留有针状物的回肠模具；所述仿生回肠材料是按照一定的质量比将制作仿生回肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的；
或所述方法为先制备具有真实回肠内部生理结构且保留有针状物的回肠模具，然后按照一定的厚度将仿生回肠原材料涂抹在回肠模具与人体回肠解剖模型相接触的一面上并静置，使仿生回肠原材料凝固成型，拔出针状物但不脱去模具，得到具有小肠绒毛且为中空的仿生回肠，再在仿生回肠不与回肠模具相接触的那一面上覆盖一层隔离物，按照一定的厚度将仿生回肠原材料涂抹在隔离物不与仿生回肠相接触的那一面上并静置，使涂抹在隔离物表面的仿生回肠原材料凝固成型，去除隔离物并脱去模具，得到具有回肠生理结构绒毛，且可分泌肠液的仿生回肠；其中，制备具有真实回肠内部生理结构且保留有针状物的回肠模具，是将可塑性材料放入并充满医学消化科精准人体回肠解剖模型，然后取下人体回肠解剖模型，再在可塑性材料的每一个与人体回肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞， 最后将针状物继续保留在可塑性材料上并对可塑性材料进行固化成型，得到具有真实回肠内部生理结构且保留有针状物的回肠模具；所述仿生回肠材料是按照一定的质量比将制作仿生回肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的；
所述基材包含硅胶、乳胶或水凝胶中的一种或多种；所述辅材包含硅油和/或固化剂。
在本发明的一种实施方式中，所述医学消化科精准人体肠道解剖模型为真实肠道1:1中空模型。
在本发明的一种实施方式中，所述可塑性材料包含陶土、石蜡、玻璃或钢铁。
在本发明的一种实施方式中，所述可塑性材料包含陶土、石蜡、玻璃或钢铁。
在本发明的一种实施方式中，所述陶土为软陶泥。
在本发明的一种实施方式中，所述制备具有真实回肠内部生理结构且保留有针状物的回肠模具，是将软陶泥放入并充满医学消化科精准人体回肠解剖模型，然后取下人体回肠解剖模型，再在软陶泥的每一个与人体回肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞，最后将针状物继续保留在软陶泥上并对软陶泥进行烤制使其固化成型，自然冷却以防止模具快速冷却产生裂缝，得到具有真实回肠内部生理结构且保留有针状物的回肠模具。
在本发明的一种实施方式中，所述烤制的时间为15～30min。
在本发明的一种实施方式中，所述小洞的直径为0.2～1mm
在本发明的一种实施方式中，所述在软陶泥的每一个与人体回肠解剖模型上小肠绒毛相对应的凹陷处戳出小洞时，应使针状物穿透软陶泥并使针状物的一端超出软陶泥与人体回肠解剖模型相接触的那一面至少2mm。
在本发明的一种实施方式中，所述回肠模具的直径为1.5～2.5cm，长度20～30cm。
在本发明的一种实施方式中，所述基材、硅油以及固化剂之间的质量比为100:(2.5～3.5):(0.5～1.5)。
在本发明的一种实施方式中，所述基材与辅材之间的质量比为100:3:1。
在本发明的一种实施方式中，所述基材为硅胶。
在本发明的一种实施方式中，所述硅胶为透明硅胶或半透明硅胶。
在本发明的一种实施方式中，所述固化剂包含正硅酸乙酯、乙烯基三胺、DETA氨乙基哌嗪AE、间苯二胺m-PDAMPD、二氨基二苯基甲烷DDM或HT-972DEH-50中的一种或多种。
在本发明的一种实施方式中，所述抽真空排泡的条件为真空机负压-0.1～0.09MPa、时间5～10min。
在本发明的一种实施方式中，所述抽真空排泡的条件为真空机负压0.09MPa、时间7min。
在本发明的一种实施方式中，所述仿生回肠原材料涂抹在回肠模具表面的厚度为2～3mm。
在本发明的一种实施方式中，所述仿生回肠原材料涂抹在回肠模具表面的厚度为2.5mm。
在本发明的一种实施方式中，所述静置的时间为2～4h。
在本发明的一种实施方式中，所述静置的时间为3h。
在本发明的一种实施方式中，所述隔离物包含油性纸或保鲜膜。
在本发明的一种实施方式中，所述仿生回肠原材料涂抹在隔离物表面表面的厚度为2～3mm。
在本发明的一种实施方式中，所述仿生回肠原材料涂抹在隔离物表面表面的厚度为2.5mm。
本发明提供了应用上述方法制备得到的仿生回肠。
本发明提供了一种仿生十二指肠的制备方法，所述方法为先制备具有真实十二指肠内部生理结构且保留有针状物的回肠模具，然后按照一定的厚度将仿生十二指肠原材料涂抹在十二指肠模具与人体十二指肠解剖模型相接触的一面上并静置，使仿生十二指肠原材料凝固成型，拔出针状物且脱去模具，得到具有小肠绒毛且为中空的仿生十二指肠；其中，制备具有真实十二指肠内部生理结构且保留有针状物的十二指肠模具，是将可塑性材料放入并充满医学消化科精准人体十二指肠解剖模型，然后取下人体十二指肠解剖模型，再在可塑性材料的每一个与人体十二指肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞，最后将针状物继续保留在可塑性材料上并对可塑性材料进行固化成型，得到具有真实十二指肠内部生理结构且保留有针状物的十二指肠模具；所述仿生十二指肠材料是按照一定的质量比将制作仿生十二指肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的；
或所述方法为先制备具有真实十二指肠内部生理结构且保留有针状物的回肠模具，然后按照一定的厚度将仿生十二指肠原材料涂抹在十二指肠模具与人体十二指肠解剖模型相接触的一面上并静置，使仿生十二指肠原材料凝固成型，拔出针状物但不脱去模具，得到具有小肠绒毛且为中空的仿生十二指肠，再在仿生十二指肠不与十二指肠模具相接触的那一面上覆盖一层隔离物，按照一定的厚度将仿生十二指肠原材料涂抹在隔离物不与仿生十二指肠相接触的那一面上并静置，使涂抹在隔离物表面的仿生十二指肠原材料凝固成型，去除隔离物并脱去模具，得到具有十二指肠生理结构绒毛，且可分泌肠液的仿生十二指肠；其中，制备具 有真实十二指肠内部生理结构且保留有针状物的十二指肠模具，是将可塑性材料放入并充满医学消化科精准人体十二指肠解剖模型，然后取下人体十二指肠解剖模型，再在可塑性材料的每一个与人体十二指肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞，最后将针状物继续保留在可塑性材料上并对可塑性材料进行固化成型，得到具有真实十二指肠内部生理结构且保留有针状物的回肠模具；所述仿生十二指肠材料是按照一定的质量比将制作仿生十二指肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的；
所述基材包含硅胶、乳胶或水凝胶中的一种或多种；所述辅材包含硅油和/或固化剂。
在本发明的一种实施方式中，所述医学消化科精准人体肠道解剖模型为真实肠道1:1中空模型。
在本发明的一种实施方式中，所述可塑性材料包含陶土、石蜡、玻璃或钢铁。
在本发明的一种实施方式中，所述可塑性材料包含陶土、石蜡、玻璃或钢铁。
在本发明的一种实施方式中，所述陶土为软陶泥。
在本发明的一种实施方式中，所述制备具有真实十二指肠内部生理结构且保留有针状物的十二指肠模具，是将软陶泥放入并充满医学消化科精准人体十二指肠解剖模型，然后取下人体十二指肠解剖模型，再在软陶泥的每一个与人体十二指肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞，最后将针状物继续保留在软陶泥上并对软陶泥进行烤制使其固化成型，自然冷却以防止模具快速冷却产生裂缝，得到具有真实十二指肠内部生理结构且保留有针状物的回肠模具。
在本发明的一种实施方式中，所述烤制的时间为15～30min。
在本发明的一种实施方式中，所述小洞的直径为0.2～1mm
在本发明的一种实施方式中，所述在软陶泥的每一个与人体十二指肠解剖模型上小肠绒毛相对应的凹陷处戳出小洞时，应使针状物穿透软陶泥并使针状物的一端超出软陶泥与人体十二指肠解剖模型相接触的那一面至少2mm。
在本发明的一种实施方式中，所述十二指肠模具的直径为3～4cm，长度20～30cm。
在本发明的一种实施方式中，所述基材、硅油以及固化剂之间的质量比为100:(0.5～1.5):(2.5～3.5)。
在本发明的一种实施方式中，所述基材与辅材之间的质量比为100:1:3。
在本发明的一种实施方式中，所述基材为硅胶。
在本发明的一种实施方式中，所述硅胶为透明硅胶或半透明硅胶。
在本发明的一种实施方式中，所述固化剂包含正硅酸乙酯、乙烯基三胺、DETA氨乙基 哌嗪AE、间苯二胺m-PDAMPD、二氨基二苯基甲烷DDM或HT-972DEH-50中的一种或多种。
在本发明的一种实施方式中，所述抽真空排泡的条件为真空机负压-0.1～0.09MPa、时间5～10min。
在本发明的一种实施方式中，所述抽真空排泡的条件为真空机负压0.09MPa、时间7min。
在本发明的一种实施方式中，所述仿生十二指肠原材料涂抹在十二指肠模具表面的厚度为1～2mm。
在本发明的一种实施方式中，所述仿生十二指肠原材料涂抹在十二指肠模具表面的厚度为1.5mm。
在本发明的一种实施方式中，所述静置的时间为2～4h。
在本发明的一种实施方式中，所述静置的时间为3h。
在本发明的一种实施方式中，所述隔离物包含油性纸或保鲜膜。
在本发明的一种实施方式中，所述仿生十二指肠原材料涂抹在隔离物表面表面的厚度为1～5mm。
在本发明的一种实施方式中，所述仿生十二指肠原材料涂抹在隔离物表面表面的厚度为1.5mm。
本发明提供了应用上述方法制备得到的仿生十二指肠。
本发明提供了一种仿生空肠的制备方法，所述方法为先制备具有真实空肠内部生理结构且保留有针状物的空肠模具，然后按照一定的厚度将仿生空肠原材料涂抹在空肠模具与人体空肠解剖模型相接触的一面上并静置，使仿生空肠原材料凝固成型，拔出针状物且脱去模具，得到具有小肠绒毛且为中空的仿生空肠；其中，制备具有真实空肠内部生理结构且保留有针状物的空肠模具，是将可塑性材料放入并充满医学消化科精准人体空肠解剖模型，然后取下人体空肠解剖模型，再在可塑性材料的每一个与人体空肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞，最后将针状物继续保留在可塑性材料上并对可塑性材料进行固化成型，得到具有真实空肠内部生理结构且保留有针状物的空肠模具；所述仿生空肠材料是按照一定的质量比将制作仿生空肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的；
或所述方法为先制备具有真实空肠内部生理结构且保留有针状物的空肠模具，然后按照一定的厚度将仿生空肠原材料涂抹在空肠模具与人体空肠解剖模型相接触的一面上并静置，使仿生空肠原材料凝固成型，拔出针状物但不脱去模具，得到具有小肠绒毛且为中空的仿生空肠，再在仿生空肠不与空肠模具相接触的那一面上覆盖一层隔离物，按照一定的厚度将仿 生空肠原材料涂抹在隔离物不与仿生空肠相接触的那一面上并静置，使涂抹在隔离物表面的仿生空肠原材料凝固成型，去除隔离物并脱去模具，得到具有空肠生理结构绒毛，且可分泌肠液的仿生空肠；其中，制备具有真实空肠内部生理结构且保留有针状物的空肠模具，是将可塑性材料放入并充满医学消化科精准人体空肠解剖模型，然后取下人体空肠解剖模型，再在可塑性材料的每一个与人体空肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞，最后将针状物继续保留在可塑性材料上并对可塑性材料进行固化成型，得到具有真实空肠内部生理结构且保留有针状物的空肠模具；所述仿生空肠材料是按照一定的质量比将制作仿生空肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的；
所述基材包含硅胶、乳胶或水凝胶中的一种或多种；所述辅材包含硅油和/或固化剂。
在本发明的一种实施方式中，所述医学消化科精准人体肠道解剖模型为真实肠道1:1中空模型。
在本发明的一种实施方式中，所述可塑性材料包含陶土、石蜡、玻璃或钢铁。
在本发明的一种实施方式中，所述可塑性材料包含陶土、石蜡、玻璃或钢铁。
在本发明的一种实施方式中，所述陶土为软陶泥。
在本发明的一种实施方式中，所述制备具有真实空肠内部生理结构且保留有针状物的空肠模具，是将软陶泥放入并充满医学消化科精准人体空肠解剖模型，然后取下人体空肠解剖模型，再在软陶泥的每一个与人体空肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞，最后将针状物继续保留在软陶泥上并对软陶泥进行烤制使其固化成型，自然冷却以防止模具快速冷却产生裂缝，得到具有真实空肠内部生理结构且保留有针状物的空肠模具。
在本发明的一种实施方式中，所述烤制的时间为15～30min。
在本发明的一种实施方式中，所述小洞的直径为0.2～1mm
在本发明的一种实施方式中，所述在软陶泥的每一个与人体空肠解剖模型上小肠绒毛相对应的凹陷处戳出小洞时，应使针状物穿透软陶泥并使针状物的一端超出软陶泥与人体空肠解剖模型相接触的那一面至少2mm。
在本发明的一种实施方式中，所述空肠模具的直径为2～3cm，长度20～30cm。
在本发明的一种实施方式中，所述基材、硅油与固化剂之间的质量比为100:(1.5～2.5):(1.5～2.5)。
在本发明的一种实施方式中，所述基材与辅材之间的质量比为100:2:2。
在本发明的一种实施方式中，所述基材为硅胶。
在本发明的一种实施方式中，所述硅胶为透明硅胶或半透明硅胶。
在本发明的一种实施方式中，所述固化剂包含正硅酸乙酯、乙烯基三胺、DETA氨乙基哌嗪AE、间苯二胺m-PDAMPD、二氨基二苯基甲烷DDM或HT-972DEH-50中的一种或多种。
在本发明的一种实施方式中，所述抽真空排泡的条件为真空机负压-0.1～0.09MPa、时间5～10min。
在本发明的一种实施方式中，所述抽真空排泡的条件为真空机负压0.09MPa、时间7min。
在本发明的一种实施方式中，所述仿生空肠原材料涂抹在空肠模具表面的厚度为1.5～2.5mm。
在本发明的一种实施方式中，所述仿生空肠原材料涂抹在空肠模具表面的厚度为2mm。
在本发明的一种实施方式中，所述静置的时间为2～4h。
在本发明的一种实施方式中，所述静置的时间为3h。
在本发明的一种实施方式中，所述隔离物包含油性纸或保鲜膜。
在本发明的一种实施方式中，所述仿生空肠原材料涂抹在隔离物表面表面的厚度为1.5～2.5mm。
在本发明的一种实施方式中，所述仿生空肠原材料涂抹在隔离物表面表面的厚度为2mm。
本发明提供了应用上述方法制备得到的仿生空肠。
有益效果：
(1)利用本发明的仿生材料制备得到的仿生消化道性能优越，与人真实消化道的在性能上、结构上以及功能上均具有极强的一致性，可模拟食品、药品、微生物等在消化系统中的真实状态，在食品、药品的研究过程中具有极大的应用前景。
(2)利用本发明的仿生材料制备得到的仿生消化道可为透明或半透明的，能实现真实且实时的消化道内部消化状态的体外观察；
(3)利用本发明的仿生材料制备得到的仿生消化道具有无粘性、不溶于水、不与酸碱起反应、耐高低温等优势，可很好的重现消化道内的消化吸收环境；
(4)本发明的仿生胃仿真性能优越(邵尔A硬度为68±5、膨胀率为36±5％、弹性为550±50％)，且具有人真实胃内壁真实生理结构，可实现胃磨碎食物的功能，与人真实胃的在性能上、结构上以及功能上均具有极强的一致性；且本发明的仿生胃将仿生胃窦和胃体分离，分别对分离的胃窦和胃体给予一定的压力，就可实现胃体和胃窦之间的“回喷流”功能；
(5)本发明的仿生大肠仿真性能优越(邵尔A硬度为60±5、膨胀率为31±5％、弹性 为460±50％)，具有人真实大肠的形态和生理结构，可真实的模拟人大肠内的消化环境，例如，此仿生大肠的内部具有环形皱褶，可增加肠内表面积，进而可供大肠内微生物菌群更好的消化吸收食物；
(6)本发明的仿生回肠、十二指肠以及空肠仿真性能优越(回肠：邵尔A硬度为32±5、膨胀率为28±5％、弹性为220±50％；十二指肠：邵尔A硬度为40±5、膨胀率为22±5％、弹性为250±50％；空肠：邵尔A硬度为36±5、膨胀率为25±5％、弹性为250±50％)，具有人真实肠道的形态和生理结构，可真实的模拟人肠道内的消化环境；本发明的仿生回肠、十二指肠以及空肠的内部具有环形皱褶，可增加肠内表面积，进而可供回肠内微生物菌群更好的消化吸收食物；本发明的仿生回肠、十二指肠以及空肠的内部具有小肠绒毛且小肠绒毛可为双层的中空结构，若将肠液填充至中空部分即可使小肠绒毛在蠕动过程中自动分泌肠液，极大地重现肠道内的消化吸收的功能。
附图说明
图1：本发明胃底的照片；
图2：本发明胃体的照片；
图3：本发明胃窦的照片；
图4：本发明胃部的整体照片；
图5：本发明仿生回肠、十二指肠以及空肠的正面照片；
图6：本发明仿生回肠、十二指肠以及空肠的反面照片；
图7：本发明仿生回肠、十二指肠以及空肠的小肠绒毛照片。
具体实施方式
下述实施例中涉及的检测方法如下：
胃内面积检测方法：
S＝2π(r 1h 1+r 2h 2+r 3h 3)+n 1(π-1)r 1h 1+n 2(π-1)r 2h 2+n 3(π-1)r 3h 3；
其中，S为胃内面积，r 1为胃底半径，h 1为胃底高，n 1为胃底壁数量，r 2为胃体半径，h 2为胃体高，n 2为胃体壁数量，r 3为胃窦半径，h 3为胃窦高，n 3为胃窦数量。
肠面积检测方法：
S＝2πr 1h 1+n(π-1)r 2h 2；
其中，S为肠面积，r 1为肠半径，h 1为肠高，n为肠壁数量，r 2为肠壁半径，h 2为肠壁高。
食物磨碎功能检测方法：
将得到的仿生胃底、仿生胃体和仿生胃窦/仿生胃整体通过管道的法兰接口固定于胃体可 视化仿生反应器(胃体可视化仿生反应器参见公开号为CN108088966A的发明专利)中，取100g生大米，粒径约1mm，加入到仿生胃中，运行反应器10min，取出大米，观察粒径是否变小。
回喷流功能检测方法：
将仿生胃固定于胃体可视化仿生反应器(胃体可视化仿生反应器参见公开号为CN108088966A的发明专利)中，加入100ml牛奶，通过运行反应器，打开反应器水流电磁阀，给予仿生胃窦压力，看是否可实现胃窦中的牛奶回喷到胃体之间的“回喷流功能”。
透明度检测方法：
采用目测，观察硅胶是否透明、透亮，有气泡，并拉伸一下硅胶，看是否发白，发白的是不透明的，将大米、玉米等食物放入硅胶内部中，看是否可清晰的看到食物的外观。
若可清晰看到食物的表面，则透明度好；若可看到食物的轮廓，则透明度适中；若看不到食物的物象，则透明度差。
硬度(邵尔硬度)检测方法：
用邵尔硬度计进行测定，以硬度计的压针压在胃的表面，测量压针压入胃表面的深度。
膨胀率检测方法：
Pe＝(W*m/A)×100％；
其中，Pe为膨胀率，W为总平衡荷重，A为硅胶面积，m为加压设备的杠杆比。
弹性检测方法：
在拉力试验机上对硅胶进行拉伸测试，测量硅胶轴向伸长量和横向伸长量，直到硅胶断裂为止。
C＝(D-d)×100％/d；
其中，C为弹性率，D为伸长量，d为硅胶初长量。
绒毛分泌肠液功能检测：
将得到的仿生十二指肠通过管道的法兰接口固定于肠道可视化仿生反应器中(肠道可视化仿生反应器参见公开号为CN108318625A的发明专利)，加入100ml胰液到硅胶仿生十二指肠中，运行反应器10min，观察分泌胰液的体积。
实施例1.1：仿生胃的制备
(1)准备陶泥：将软陶泥反复揉捏，得到延展性较好的软陶泥；
(2)胃底模具压制：将揉好的软陶泥进行放入医学消化科精准人体胃解剖模型胃底中，用力挤压，取下人体胃解剖模型，得到具有真实胃底内部生理结构的软陶泥胃底模具；
(3)胃底模具烤制成型：将胃底模具放入烤箱烤制15分钟，使胃底模具固化成型，自然冷却，得到仿生胃底模具；
(4)胃体模具压制：将揉好的软陶泥进行放入医学消化科精准人体胃解剖模型胃体中，用力挤压，取下人体胃解剖模型，得到具有真实胃体内部生理结构的软陶泥胃体模具；
(5)胃体模具烤制成型：将胃体模具放入烤箱烤制15分钟，使胃体模具固化成型，自然冷却，得到仿生胃体模具；
(6)胃窦模具压制：将揉好的软陶泥进行放入医学消化科精准人体胃解剖模型胃窦中，用力挤压，取下人体胃解剖模型，得到具有真实胃窦内部生理结构的软陶泥胃窦模具；
(7)胃窦模具烤制成型：将胃窦模具放入烤箱烤制15分钟，使胃窦模具固化成型，自然冷却，得到仿生胃窦模具；
(8)准备硅胶：将按100:8:2的透明硅胶、硅油和固化剂正硅酸乙酯置于烧杯中，充分搅拌，混合均匀；
(9)将混合均匀的硅胶放入真空机中，负压0.09MPa，抽真空排泡，时间5分钟，得到无气泡硅胶；
(10)将上述得到的仿生胃底、胃体、胃窦模具表面均匀涂抹无气泡硅胶，厚度约1mm；
(11)将涂抹均匀的三种模具静置2小时，使其彻底凝固成型，脱去模具后，再经过一定的修剪处理，得到硅胶仿生胃底、硅胶仿生胃体和硅胶仿生胃窦。
实施例1.2：仿生胃的制备
在实施例1.1的基础上，将步骤(3)、(5)、(7)中的模具烤制时间变为20分钟；将步骤(8)中的固化剂变为二氨基二苯基甲烷DDM，同时将透明硅胶、硅油和固化剂的质量比变为100:7:1.5；将步骤(9)中的排泡时间变为10分钟；将步骤(10)中的涂抹厚度变为2mm；将步骤(11)中的静置时间变为4小时。
实施例1.3：仿生胃的制备
在实施例1.1的基础上，将步骤(3)、(5)、(7)中的模具烤制时间变为30分钟；将步骤(8)中的固化剂变为乙烯基三胺，同时将透明硅胶、硅油和固化剂的质量比变为100:9:3；将步骤(10)中的涂抹厚度变为3mm；将步骤(11)中的静置时间变为1小时。
对比例1.1：仿生胃的制备(无胃内部生物结构)
在实施例1.1的基础上，将步骤(2)变为：将揉好的软陶泥做成表面光滑的胃底形状，得到胃底模具；将步骤(4)变为：将揉好的软陶泥做成表面光滑的胃体形状，得到胃体模具；将步骤(6)变为：将揉好的软陶泥做成光滑的胃窦形状，得到胃窦模具；将步骤(3)、(5)、 (7)中的模具烤制时间变为30分钟；将步骤(8)中的透明硅胶、硅油和固化剂的质量比变为100:5:2；将步骤(10)中的涂抹厚度变为2mm。
对比例1.2：仿生胃的制备(胃整体模型)
在实施例1.1的基础上，将步骤(2)-(7)变为：先将揉好的软陶泥做成表面光滑的胃形状，得到胃底模具，再将胃模具放入烤箱烤制30分钟，使胃模具固化成型，自然冷却，得到胃模具；将步骤(8)中的透明硅胶、硅油和固化剂的质量比变为100:6:1；将步骤(10)中的涂抹厚度变为2mm。
对比例1.3：仿生胃的制备(混合后硅胶不抽真空)
在实施例1.1的基础上，将步骤(3)、(5)、(7)中的模具烤制时间变为30分钟；将步骤(8)中透明硅胶、硅油和固化剂的质量比变为100:10:3；省略步骤(9)；将步骤(10)中的涂抹厚度变为3mm；将步骤(11)中的静置时间变为1小时。
对比例1.4：仿生胃的制备(涂抹硅胶厚度增加)
在实施例1.1的基础上，将步骤(3)、(5)、(7)中的模具烤制时间变为30分钟；将步骤(8)中透明硅胶、硅油和固化剂的质量比变为100:8:2；省略步骤(9)；将步骤(10)中的涂抹厚度变为6mm；将步骤(11)中的静置时间变为1小时。
对比例1.5：仿生胃的制备(不添加硅油)
在实施例1.1的基础上，将步骤(3)、(5)、(7)中的模具烤制时间变为30分钟；将步骤(8)中的硅油省略，同时将透明硅胶和固化剂的质量比变为100:3；将步骤(10)中的涂抹厚度变为2mm；将步骤(11)中的静置时间变为1小时。
对比例1.6：仿生胃的制备(添加甘油)
在实施例1.1的基础上，将步骤(3)、(5)、(7)中的模具烤制时间变为30分钟；将步骤(8)中的硅油替换为甘油；将步骤(10)中的涂抹厚度变为2mm；将步骤(11)中的静置时间变为1小时。
实施例1.4：仿生胃的检测
将人体胃解剖模型、实施例1.1-1.3制备得到的仿生胃、对比例1.1-1.6制备得到的仿生胃以及国外同类产品(购自美国Dragon Skin公司的Fast 10型号的硅胶仿生胃)进行胃内面积、食物磨碎功能、回喷流功能、透明度、硬度、膨胀率以及弹性检测，检测结果如表1。
由表1可知，本发明的仿生胃与真实胃的指标对比较为接近，与国外同类产品对比，指标较优，因此，本发明的仿生胃可替代真实胃来预测活体试验，完全代替或部分代替活体试验，达到降低成本和时间、提高重复性和准确性的目的，而且没有理论的限制。
表1性能检测结果
Figure PCTCN2018117135-appb-000001
实施例2.1：仿生大肠的制备
(1)准备陶泥：将软陶泥反复揉捏，得到延展性较好的软陶泥；
(2)大肠模具压制：将揉好的软陶泥进行放入医学消化科精准人体大肠解剖模型中，用力挤压，取下人体大肠解剖模型，得到具有真实大肠内部生理结构的软陶泥大肠模具，模具直径4cm，长度25cm；
(3)大肠模具烤制成型：将大肠模具放入烤箱140℃烤制15分钟，使大肠模具固化成型，自然冷却，得到仿生大肠模具；
(4)准备硅胶：将按100:5:2的透明硅胶、硅油和固化剂正硅酸乙酯置于烧杯中，充分搅拌，混合均匀；
(5)将混合均匀的硅胶放入真空机中，负压0.09MPa，抽真空排泡，时间5分钟，得到无气泡硅胶；
(6)将上述得到的仿生大肠模具表面均匀涂抹无气泡硅胶，厚度约1mm；
(7)将涂抹均匀的大肠模具静置2小时，使其彻底凝固成型；
(8)将硅胶脱去大肠模具后，再经过一定的修剪处理，可得到具有大肠生理结构肠壁皱褶的仿生大肠硅胶模型。
实施例2.2：仿生大肠的制备
在实施例2.1的基础上，将步骤(2)中的模具直径变为4.5cm；将步骤(4)中的固化剂替换为乙烯基三胺，同时将透明硅胶、硅油和固化剂的质量比变为100:4:1；将步骤(6)中的涂抹厚度变为2mm；将步骤(7)中的静置时间变为4小时。
实施例2.3：仿生大肠的制备
在实施例2.1的基础上，将步骤(2)中的模具直径变为5cm；将步骤(4)中的固化剂替换为二氨基二苯基甲烷DDM，同时将透明硅胶、硅油和固化剂的质量比变为100:6:3；将步骤(6)中的涂抹厚度变为3mm。
对比例2.1：仿生大肠的制备(无皱褶)
在实施例2.1的基础上，将步骤(2)变为：将揉好的软陶泥揉成表面光滑的长柱体，模具直径4cm，长度30cm；将步骤(3)中的烤制条件变为130℃烤制30分钟；将步骤(4)中透明硅胶、硅油和固化剂的质量比变为100:5:3；将步骤(6)中的涂抹厚度变为2mm；将步骤(7)中的静置时间变为1小时。
对比例2.2：仿生大肠的制备(混合后硅胶不抽真空)
在实施例2.1的基础上，将步骤(2)中的模具直径变为4.5cm；将步骤(3)中的烤制条件变为130℃烤制30分钟；将步骤(4)中透明硅胶、硅油和固化剂的质量比变为100:6:2；省略步骤(5)；将步骤(6)中的涂抹厚度变为2mm。
对比例2.3：仿生大肠的制备(涂抹硅胶厚度增加)
在实施例2.1的基础上，将步骤(2)中的模具直径变为5cm；将步骤(3)中的烤制条件变为130℃烤制30分钟；将步骤(4)中的固化剂替换为乙烯基三胺，同时将透明硅胶、硅油和固化剂的质量比变为100:3:3；将步骤(6)中的涂抹厚度变为8mm。
对比例2.4：仿生大肠的制备(不添加硅油)
在实施例2.1的基础上，将步骤(2)中的模具直径变为5cm；将步骤(3)中的烤制条件变为150℃烤制15分钟；将步骤(4)中的硅油省略，同时将透明硅胶固化剂的质量比变为100:3；将步骤(6)中的涂抹厚度变为2mm。
对比例2.5：仿生大肠的制备(添加甘油)
在实施例2.1的基础上，将步骤(2)中的模具直径变为5cm；将步骤(3)中的烤制条件变为150℃烤制15分钟；将步骤(4)中的硅油替换为甘油；将步骤(6)中的涂抹厚度变 为2mm。
实施例2.4：仿生大肠的检测
取同长度的人体大肠解剖模型、实施例2.1-2.3制备得到的仿生大肠、对比例2.1-2.5制备得到的仿生大肠以及国外同类产品(购自美国Dragon Skin公司的Fast 6型号的硅胶仿生大肠)进行肠面积、透明度、硬度、膨胀率以及弹性检测，检测结果如表2。
由表2可知，本发明的仿生大肠与真实大肠的指标对比较为接近，与国外同类产品对比，指标较优，因此，本发明的仿生大肠可替代真实大肠来预测活体试验，完全代替或部分代替活体试验，达到降低成本和时间、提高重复性和准确性的目的，而且没有理论的限制。
表2性能检测结果
  肠面积 透明效果 硬度 膨胀率 弹性
人体大肠解剖模型 ＞600cm 2 不透明 61 30％ 420％
实施例1 ＞600cm 2 好 60 31％ 460％
实施例2 ＞600cm 2 好 58 29％ 430％
实施例3 ＞600cm 2 好 63 31％ 470％
对比例1 ＜200cm 2 好 64 30％ 490％
对比例2 ＞600cm 2 较差，有气泡 59 33％ 430％
对比例3 ＞600cm 2 差 63 28％ 420％
对比例4 ＞600cm 2 好 71 10％ 520％
对比例5 ＞600cm 2 好 58 20％ 550％
国外同类产品 ＜200cm 2 好 30 10％ 1000％
实施例3.1：仿生回肠的制备
(1)准备陶泥：将软陶泥反复揉捏，得到延展性较好的软陶泥；
(2)回肠模具压制：将揉好的软陶泥进行放入医学消化科精准人体回肠解剖模型中，用力挤压，取下人体回肠解剖模型，得到具有真实回肠内部生理结构的软陶泥回肠模具，模具直径1.5cm，长度25cm；
(3)中空绒毛制作：取直径为0.5mm针若干，扎在上述模具上的每一个印记处，戳直径1mm，深5mm的小洞，针继续保留在模具内部
(4)回肠模具烤制成型：将回肠模具放入烤箱140℃烤制15分钟，使回肠模具固化成型，自然冷却，得到仿生回肠模具；
(5)准备硅胶：将按100:3:1的透明硅胶、硅油与固化剂正硅酸乙酯置于烧杯中，充分 搅拌，混合均匀；
(6)将混合均匀的硅胶放入真空机中，负压0.09MPa，抽真空排泡，时间5分钟，得到无气泡硅胶；
(7)将上述得到的仿生回肠模具表面均匀涂抹无气泡硅胶，厚度约2mm；
(8)将涂抹均匀的回肠模具静置2小时，使其彻底凝固成型后，将模具外的针拔掉，得到具有小肠绒毛且为中空的回肠硅胶模型；
(9)将上述仅拔掉针，未脱落硅胶的回肠模具表面覆盖一张油性纸，外侧放置一直径为2cm，高4cm的空心圆柱体，固定粘好；
(10)将回肠模具的油性纸和圆柱体之间的空隙均匀涂抹无气泡的硅胶，静置2小时，待其彻底凝固成型；
(11)将凝固好的硅胶模具放置于水中10分钟，待水将油性纸软化后，将油性纸从空心圆柱体中取出；
(12)将硅胶脱去回肠模具后，再经过一定的修剪处理，可得到具有回肠生理结构肠壁皱褶和绒毛，且绒毛可分泌肠液的仿生回肠硅胶模型。
实施例3.2：仿生回肠的制备
在实施例3.1的基础上，将步骤(2)中的模具直径变为2cm；将步骤(3)中针的直径变为0.3mm，小洞的直径变为0.5mm；将步骤(4)的烤制条件变为150℃烤制20分钟；将步骤(5)中的固化剂变为乙烯基三胺，同时将透明硅胶、硅油与固化剂的质量比变为100:3:1.5；将步骤(7)中的涂抹厚度变为2.5mm；将步骤(8)中的静置时间变为4小时；将步骤(10)中的静置时间变为1小时。
实施例3.3：仿生回肠的制备
在实施例3.1的基础上，将步骤(2)中的模具直径变为2.5cm，长度变为30cm；将步骤(3)中针的直径变为0.1mm，小洞的直径变为0.2mm；将步骤(4)的烤制条件变为130℃烤制30分钟；将步骤(5)中的固化剂变为二氨基二苯基甲烷DDM，同时将透明硅胶、硅油与固化剂的质量比变为100:2.5:1；将步骤(7)中的涂抹厚度变为3mm；将步骤(8)中的静置时间变为1小时；将步骤(10)中的静置时间变为1小时。
对比例3.1：仿生回肠的制备(无绒毛)
在实施例3.1的基础上，将步骤(2)中的模具直径变为2.5cm，长度变为30cm；省略步骤(3)；将步骤(4)的烤制条件变为130℃烤制30分钟；将步骤(5)中透明硅胶、硅油与固化剂的质量比变为100:3.5:0.5；将步骤(7)中的涂抹厚度变为2.5mm；将步骤(8)变 为：将涂抹均匀的回肠模具静置1小时，使其彻底凝固成型；省略步骤(9)-(11)。
对比例3.2：仿生回肠的制备(混合后硅胶不抽真空)
在实施例3.1的基础上，将步骤(2)中的模具直径变为2cm，长度变为30cm；将步骤(3)中针的直径变为0.2mm，小洞的直径变为0.5mm；将步骤(4)的烤制条件变为140℃烤制20分钟；将步骤(5)中透明硅胶、硅油与固化剂的质量比变为100:3:0.5；省略步骤(6)；将步骤(7)中的涂抹厚度变为2.5mm。
对比例3.3：仿生回肠的制备(涂抹硅胶厚度增加)
在实施例3.1的基础上，将步骤(2)中的模具直径变为2cm，长度变为30cm；将步骤(3)中针的直径变为0.4mm，小洞的直径变为0.6mm；将步骤(4)的烤制条件变为130℃烤制30分钟；将步骤(5)中透明硅胶、硅油与固化剂的质量比变为100:2.5:1.5；将步骤(7)中的涂抹厚度变为6mm。
对比例3.4：仿生回肠的制备(不添加硅油)
在实施例3.1的基础上，将步骤(2)中的模具直径变为2cm，长度变为30cm；将步骤(3)中针的直径变为0.4mm，小洞的直径变为0.6mm；将步骤(4)的烤制条件变为130℃烤制30分钟；将步骤(5)中的硅油省略。
对比例3.5：仿生回肠的制备(添加甘油)
在实施例3.1的基础上，将步骤(2)中的模具直径变为2cm，长度变为30cm；将步骤(3)中针的直径变为0.4mm，小洞的直径变为0.6mm；将步骤(4)的烤制条件变为130℃烤制30分钟；将步骤(5)中的硅油替换为甘油。
实施例3.4：仿生回肠的检测
取同长度的人体回肠解剖模型、实施例3.1-3.3制备得到的仿生回肠、对比例3.1-3.5制备得到的仿生回肠以及国外同类产品(购自美国Dragon Skin公司的Fast 3型号的硅胶仿生回肠)进行肠面积、透明度、硬度、膨胀率、弹性检测以及绒毛功能检测，检测结果如表3。
由表3可知，本发明的仿生回肠与真实回肠的指标对比较为接近，与国外同类产品对比，指标较优，因此，本发明的仿生回肠可替代真实回肠来预测活体试验，完全代替或部分代替活体试验，达到降低成本和时间、提高重复性和准确性的目的，而且没有理论的限制。
表3性能检测结果
Figure PCTCN2018117135-appb-000002
Figure PCTCN2018117135-appb-000003
实施例4.1：仿生十二指肠的制备
(1)准备陶泥：将软陶泥反复揉捏，得到延展性较好的软陶泥；
(2)十二指肠模具压制：将揉好的软陶泥进行放入医学消化科精准人体十二指肠解剖模型中，用力挤压，取下人体十二指肠解剖模型，得到具有真实十二指肠内部生理结构的软陶泥十二指肠模具，模具直径3cm，长度25cm；
(3)中空绒毛制作：取直径为0.5mm针若干，扎在上述模具上的每一个印记处，戳直径1mm，深5mm的小洞，针继续保留在模具内部
(4)十二指肠模具烤制成型：将十二指肠模具放入烤箱140℃烤制15分钟，使十二指肠模具固化成型，自然冷却，得到仿生十二指肠模具；
(5)准备硅胶：将按100:1:3的透明硅胶、硅油和固化剂正硅酸乙酯置于烧杯中，充分搅拌，混合均匀；
(6)将混合均匀的硅胶放入真空机中，负压0.09MPa，抽真空排泡，时间5分钟，得到无气泡硅胶；
(7)将上述得到的仿生十二指肠模具表面均匀涂抹无气泡硅胶，厚度约1mm；
(8)将涂抹均匀的十二指肠模具静置2小时，使其彻底凝固成型后，将模具外的针拔掉，得到具有小肠绒毛且为中空的十二指肠硅胶模型；
(9)将上述仅拔掉针，未脱落硅胶的十二指肠模具表面覆盖一张油性纸，外侧放置一直径为2cm，高4cm的空心圆柱体，固定粘好；
(10)将十二指肠模具的油性纸和圆柱体之间的空隙均匀涂抹无气泡的硅胶，静置2小时，待其彻底凝固成型；
(11)将凝固好的硅胶模具放置于水中10分钟，待水将油性纸软化后，将油性纸从空心 圆柱体中取出；
(12)将硅胶脱去十二指肠模具后，再经过一定的修剪处理，可得到具有十二指肠生理结构肠壁皱褶和绒毛，且绒毛可分泌肠液的仿生十二指肠硅胶模型。
实施例4.2：仿生十二指肠的制备
在实施例4.1的基础上，将步骤(2)中的模具直径变为3.5cm；将步骤(3)中针的直径变为0.3mm，小洞的直径变为0.5mm；将步骤(4)的烤制条件变为150℃烤制20分钟；将步骤(5)中的固化剂变为乙烯基三胺，同时将透明硅胶、硅油与固化剂的质量比变为100:1.5:3；将步骤(7)中的涂抹厚度变为1.5mm；将步骤(8)中的静置时间变为4小时；将步骤(10)中的静置时间变为1小时。
实施例4.3：仿生十二指肠的制备
在实施例4.1的基础上，将步骤(2)中的模具直径变为4cm，长度变为30cm；将步骤(3)中针的直径变为0.1mm，小洞的直径变为0.2mm；将步骤(4)的烤制条件变为130℃烤制30分钟；将步骤(5)中的固化剂变为二氨基二苯基甲烷DDM，同时将透明硅胶、硅油与固化剂的质量比变为100:1:2.5；将步骤(7)中的涂抹厚度变为2mm；将步骤(8)中的静置时间变为1小时；将步骤(10)中的静置时间变为1小时。
对比例4.1：仿生十二指肠的制备(无绒毛)
在实施例4.1的基础上，将步骤(2)中的模具长度变为30cm；省略步骤(3)；将步骤(4)的烤制条件变为130℃烤制30分钟；将步骤(5)中透明硅胶、硅油与固化剂的质量比变为100:1:3；将步骤(7)中的涂抹厚度变为1.5mm；将步骤(8)变为：将涂抹均匀的回肠模具静置1小时，使其彻底凝固成型；省略步骤(9)-(11)。
对比例4.2：仿生十二指肠的制备(混合后硅胶不抽真空)
在实施例4.1的基础上，将步骤(2)中的模具直径变为3.5cm，长度变为30cm；将步骤(3)中针的直径变为0.2mm，小洞的直径变为0.5mm；将步骤(4)的烤制条件变为140℃烤制20分钟；将步骤(5)中透明硅胶、硅油与固化剂的质量比变为100:0.5:2.5；省略步骤(6)；将步骤(7)中的涂抹厚度变为1.5mm。
对比例4.3：仿生十二指肠的制备(涂抹硅胶厚度增加)
在实施例4.1的基础上，将步骤(2)中的模具直径变为4cm，长度变为30cm；将步骤(3)中针的直径变为0.4mm，小洞的直径变为0.6mm；将步骤(4)的烤制条件变为130℃烤制30分钟；将步骤(5)中透明硅胶、硅油与固化剂的质量比变为100:1.5:3.5；将步骤(7)中的涂抹厚度变为6mm。
对比例4.4：仿生十二指肠的制备(不添加硅油)
在实施例4.1的基础上，将步骤(2)中的模具直径变为4cm，长度变为30cm；将步骤(3)中针的直径变为0.4mm，小洞的直径变为0.6mm；将步骤(4)的烤制条件变为130℃烤制30分钟；将步骤(5)中的硅油省略。
对比例4.5：仿生十二指肠的制备(添加甘油)
在实施例4.1的基础上，将步骤(2)中的模具直径变为4cm，长度变为30cm；将步骤(3)中针的直径变为0.4mm，小洞的直径变为0.6mm；将步骤(4)的烤制条件变为130℃烤制30分钟；将步骤(5)中的硅油替换为甘油。
实施例4.4：仿生十二指肠的检测
取同长度的人体十二指肠解剖模型、实施例4.1-4.3制备得到的仿生十二指肠、对比例4.1-4.5制备得到的仿生十二指肠以及国外同类产品(购自美国Dragon Skin公司的Fast 8型号的硅胶仿生十二指肠)进行肠面积、透明度、硬度、膨胀率、弹性以及绒毛功能检测，检测结果如表4。
由表4可知，本发明的仿生十二指肠与真实十二指肠的指标对比较为接近，与国外同类产品对比，指标较优，因此，本发明的仿生十二指肠可替代真实十二指肠来预测活体试验，完全代替或部分代替活体试验，达到降低成本和时间、提高重复性和准确性的目的，而且没有理论的限制。
表4性能检测结果
Figure PCTCN2018117135-appb-000004
Figure PCTCN2018117135-appb-000005
实施例5.1：仿生空肠的制备
(1)准备陶泥：将软陶泥反复揉捏，得到延展性较好的软陶泥；
(2)空肠模具压制：将揉好的软陶泥进行放入医学消化科精准人体空肠解剖模型中，用力挤压，取下人体空肠解剖模型，得到具有真实空肠内部生理结构的软陶泥空肠模具，模具直径2cm，长度25cm；
(3)中空绒毛制作：取直径为0.5mm针若干，扎在上述模具上的每一个印记处，戳直径1mm，深5mm的小洞，针继续保留在模具内部
(4)空肠模具烤制成型：将空肠模具放入烤箱140℃烤制15分钟，使空肠模具固化成型，自然冷却，得到仿生空肠模具；
(5)准备硅胶：将按100:2:2的透明硅胶、硅油与固化剂正硅酸乙酯置于烧杯中，充分搅拌，混合均匀；
(6)将混合均匀的硅胶放入真空机中，负压0.09MPa，抽真空排泡，时间5分钟，得到无气泡硅胶；
(7)将上述得到的仿生空肠模具表面均匀涂抹无气泡硅胶，厚度约1.5mm；
(8)将涂抹均匀的空肠模具静置2小时，使其彻底凝固成型后，将模具外的针拔掉，得到具有小肠绒毛且为中空的空肠硅胶模型；
(9)将上述仅拔掉针，未脱落硅胶的空肠模具表面覆盖一张油性纸，外侧放置一直径为2cm，高4cm的空心圆柱体，固定粘好；
(10)将空肠模具的油性纸和圆柱体之间的空隙均匀涂抹无气泡的硅胶，静置2小时，待其彻底凝固成型；
(11)将凝固好的硅胶模具放置于水中10分钟，待水将油性纸软化后，将油性纸从空心圆柱体中取出；
(12)将硅胶脱去空肠模具后，再经过一定的修剪处理，可得到具有空肠生理结构肠壁皱褶和绒毛，且绒毛可分泌肠液的仿生空肠硅胶模型。
实施例5.2：仿生空肠的制备
在实施例5.1的基础上，将步骤(2)中的模具直径变为2.5cm；将步骤(3)中针的直径变为0.3mm，小洞的直径变为0.5mm；将步骤(4)的烤制条件变为150℃烤制20分钟；将步骤(5)中的固化剂变为乙烯基三胺，同时将透明硅胶、硅油与固化剂的质量比变为100:1.5:2；将步骤(7)中的涂抹厚度变为2mm；将步骤(8)中的静置时间变为4小时；将步骤(10) 中的静置时间变为1小时。
实施例5.3：仿生空肠的制备
在实施例5.1的基础上，将步骤(2)中的模具直径变为3cm，长度变为30cm；将步骤(3)中针的直径变为0.1mm，小洞的直径变为0.2mm；将步骤(4)的烤制条件变为130℃烤制30分钟；将步骤(5)中的固化剂变为二氨基二苯基甲烷DDM，同时将透明硅胶、硅油与固化剂的质量比变为100:2:2.5；将步骤(7)中的涂抹厚度变为2.5mm；将步骤(8)中的静置时间变为1小时；将步骤(10)中的静置时间变为1小时。
对比例5.1：仿生空肠的制备(无绒毛)
在实施例5.1的基础上，将步骤(2)中的模具直径变为2.5cm，长度变为30cm；省略步骤(3)；将步骤(4)的烤制条件变为130℃烤制30分钟；将步骤(5)中透明硅胶、硅油与固化剂的质量比变为100:1.5:2.5；将步骤(7)中的涂抹厚度变为2mm；将步骤(8)变为：将涂抹均匀的回肠模具静置1小时，使其彻底凝固成型；省略步骤(9)-(11)。
对比例5.2：仿生空肠的制备(混合后硅胶不抽真空)
在实施例5.1的基础上，将步骤(2)中的模具直径变为2.5cm，长度变为30cm；将步骤(3)中针的直径变为0.2mm，小洞的直径变为0.5mm；将步骤(4)的烤制条件变为140℃烤制20分钟；将步骤(5)中透明硅胶、硅油与固化剂的质量比变为100:2.5:1.5；省略步骤(6)；将步骤(7)中的涂抹厚度变为2mm。
对比例5.3：仿生空肠的制备(涂抹硅胶厚度增加)
在实施例5.1的基础上，将步骤(2)中的模具直径变为2.5cm，长度变为30cm；将步骤(3)中针的直径变为0.4mm，小洞的直径变为0.6mm；将步骤(4)的烤制条件变为130℃烤制30分钟；将步骤(5)中透明硅胶、硅油与固化剂的质量比变为100:2:2；将步骤(7)中的涂抹厚度变为6mm。
对比例5.4：仿生空肠的制备(不添加硅油)
在实施例5.1的基础上，将步骤(2)中的模具直径变为2.5cm，长度变为30cm；将步骤(3)中针的直径变为0.4mm，小洞的直径变为0.6mm；将步骤(4)的烤制条件变为130℃烤制30分钟；将步骤(5)中的硅油省略。
对比例5.5：仿生空肠的制备(添加甘油)
在实施例5.1的基础上，将步骤(2)中的模具直径变为2.5cm，长度变为30cm；将步骤(3)中针的直径变为0.4mm，小洞的直径变为0.6mm；将步骤(4)的烤制条件变为130℃烤制30分钟；将步骤(5)中的硅油替换为甘油。
实施例5.4：仿生空肠的检测
取同长度的人体空肠解剖模型、实施例5.1-5.3制备得到的仿生空肠、对比例5.1-5.5制备得到的仿生空肠以及国外同类产品(购自美国Dragon Skin公司的Fast 4型号的硅胶仿生空肠)进行肠面积、透明度、硬度、膨胀率、弹性检测以及绒毛功能检测，检测结果如表5。
由表5可知，本发明的仿生空肠与空指肠的指标对比较为接近，与国外同类产品对比，指标较优，因此，本发明的仿生空肠可替代真实空肠来预测活体试验，完全代替或部分代替活体试验，达到降低成本和时间、提高重复性和准确性的目的，而且没有理论的限制。
表5性能检测结果
Figure PCTCN2018117135-appb-000006
虽然本发明已以较佳实施例公开如上，但其并非用以限定本发明，任何熟悉此技术的人，在不脱离本发明的精神和范围内，都可做各种的改动与修饰，因此本发明的保护范围应该以权利要求书所界定的为准。

Claims (18)

  1. 一种仿生消化道，其特征在于，所述仿生消化道的成分包含基材和辅材；所述基材包含硅胶、乳胶或水凝胶中的一种或多种；所述辅材包含硅油以及固化剂；
    所述消化道包含胃、大肠、回肠、十二指肠、空肠中的一种或多种；
    所述消化道为胃时，基材、硅油以及固化剂之间的质量比为100:(5～10):(1～3)；或所述消化道为大肠时，基材、硅油以及固化剂之间的质量比为100:(3～6):(1～3)；或所述消化道为回肠时，基材、硅油以及固化剂之间的质量比为100:(2.5～3.5):(0.5～1.5)；或所述消化道为十二指肠时，基材、硅油以及固化剂之间的质量比为100:(0.5～1.5):(2.5～3.5)；或所述消化道为空肠时，基材、硅油以及固化剂之间的质量比为100:(1.5～2.5):(1.5～2.5)。
  2. 如权利要求1所述的一种仿生消化道，其特征在于，所述基材为硅胶。
  3. 如权利要求2所述的一种仿生消化道，其特征在于，所述硅胶为透明硅胶或半透明硅胶。
  4. 如权利要求1-3任一所述的一种仿生消化道，其特征在于，所述固化剂包含正硅酸乙酯、乙烯基三胺、DETA氨乙基哌嗪AE、间苯二胺m-PDAMPD、二氨基二苯基甲烷DDM或HT-972DEH-50中的一种或多种。
  5. 如权利要求1-4任一所述的一种仿生消化道，其特征在于，所述消化道为胃时，仿生胃的制备方法为先制备具有真实胃底、胃体以及胃窦内部生理结构的胃底、胃体以及胃窦模具，然后按照一定的厚度将仿生胃原材料涂抹在胃底、胃体以及胃窦模具的表面并静置，使仿生胃原材料凝固成型，脱去模具，得到仿生胃；其中，制备具有真实胃底、胃体以及胃窦内部生理结构的胃底、胃体以及胃窦模具，是将可塑性材料分别放入并充满医学消化科精准人体胃解剖模型的胃底、胃体以及胃窦，然后取下医学消化科精准人体胃解剖模型并对可塑性材料进行固化成型，得到具有真实胃底、胃体以及胃窦内部生理结构的胃底、胃体以及胃窦模具；所述仿生胃材料是按照一定的质量比将制作仿生胃的基材和辅材进行混合后放入真空机中抽真空排泡得到的；
    所述消化道为大肠时，仿生大肠的制备方法为先制备具有真实大肠内部生理结构的大肠模具，然后按照一定的厚度将仿生大肠原材料涂抹在大肠模具的表面并静置，使仿生大肠原材料凝固成型，脱去模具，得到仿生大肠；其中，制备具有真实大肠内部生理结构的大肠模具，是将可塑性材料放入并充满医学消化科精准人体肠道解剖模型大肠，然后取下医学消化科精准人体肠道解剖模型大肠并对可塑性材料进行固化成型，得到具有真实大肠内部生理结构的大肠模具；所述仿生大肠材料是按照一定的质量比将制作仿生大肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的；
    所述消化道为回肠时，仿生回肠的制备方法为先制备具有真实回肠内部生理结构且保留 有针状物的回肠模具，然后按照一定的厚度将仿生回肠原材料涂抹在回肠模具与人体回肠解剖模型相接触的一面上并静置，使仿生回肠原材料凝固成型，拔出针状物且脱去模具，得到具有小肠绒毛且为中空的仿生回肠；其中，制备具有真实回肠内部生理结构且保留有针状物的回肠模具，是将可塑性材料放入并充满医学消化科精准人体回肠解剖模型，然后取下人体回肠解剖模型，再在可塑性材料的每一个与人体回肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞，最后将针状物继续保留在可塑性材料上并对可塑性材料进行固化成型，得到具有真实回肠内部生理结构且保留有针状物的回肠模具；所述仿生回肠材料是按照一定的质量比将制作仿生回肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的；
    或所述消化道为回肠时，仿生回肠的制备方法为先制备具有真实回肠内部生理结构且保留有针状物的回肠模具，然后按照一定的厚度将仿生回肠原材料涂抹在回肠模具与人体回肠解剖模型相接触的一面上并静置，使仿生回肠原材料凝固成型，拔出针状物但不脱去模具，得到具有小肠绒毛且为中空的仿生回肠，再在仿生回肠不与回肠模具相接触的那一面上覆盖一层隔离物，按照一定的厚度将仿生回肠原材料涂抹在隔离物不与仿生回肠相接触的那一面上并静置，使涂抹在隔离物表面的仿生回肠原材料凝固成型，去除隔离物并脱去模具，得到具有回肠生理结构绒毛，且可分泌肠液的仿生回肠；其中，制备具有真实回肠内部生理结构且保留有针状物的回肠模具，是将可塑性材料放入并充满医学消化科精准人体回肠解剖模型，然后取下人体回肠解剖模型，再在可塑性材料的每一个与人体回肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞，最后将针状物继续保留在可塑性材料上并对可塑性材料进行固化成型，得到具有真实回肠内部生理结构且保留有针状物的回肠模具；所述仿生回肠材料是按照一定的质量比将制作仿生回肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的；
    所述消化道为十二指肠时，仿生十二指肠的制备方法为先制备具有真实十二指肠内部生理结构且保留有针状物的回肠模具，然后按照一定的厚度将仿生十二指肠原材料涂抹在十二指肠模具与人体十二指肠解剖模型相接触的一面上并静置，使仿生十二指肠原材料凝固成型，拔出针状物且脱去模具，得到具有小肠绒毛且为中空的仿生十二指肠；其中，制备具有真实十二指肠内部生理结构且保留有针状物的十二指肠模具，是将可塑性材料放入并充满医学消化科精准人体十二指肠解剖模型，然后取下人体十二指肠解剖模型，再在可塑性材料的每一个与人体十二指肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞，最后将针状物继续保留在可塑性材料上并对可塑性材料进行固化成型，得到具有真实十二指肠内部生理结构且保留有针状物的十二指肠模具；所述仿生十二指肠材料是按照一定的质量比将制作仿生十二指肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的；
    或所述消化道为十二指肠时，仿生十二指肠的制备方法为先制备具有真实十二指肠内部生理结构且保留有针状物的回肠模具，然后按照一定的厚度将仿生十二指肠原材料涂抹在十二指肠模具与人体十二指肠解剖模型相接触的一面上并静置，使仿生十二指肠原材料凝固成型，拔出针状物但不脱去模具，得到具有小肠绒毛且为中空的仿生十二指肠，再在仿生十二指肠不与十二指肠模具相接触的那一面上覆盖一层隔离物，按照一定的厚度将仿生十二指肠原材料涂抹在隔离物不与仿生十二指肠相接触的那一面上并静置，使涂抹在隔离物表面的仿生十二指肠原材料凝固成型，去除隔离物并脱去模具，得到具有十二指肠生理结构绒毛，且可分泌肠液的仿生十二指肠；其中，制备具有真实十二指肠内部生理结构且保留有针状物的回肠模具，是将可塑性材料放入并充满医学消化科精准人体十二指肠解剖模型，然后取下人体十二指肠解剖模型，再在可塑性材料的每一个与人体十二指肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞，最后将针状物继续保留在可塑性材料上并对可塑性材料进行固化成型，得到具有真实十二指肠内部生理结构且保留有针状物的十二指肠模具；所述仿生十二指肠材料是按照一定的质量比将制作仿生十二指肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的；
    所述消化道为空肠时，仿生空肠的制备方法为先制备具有真实空肠内部生理结构且保留有针状物的空肠模具，然后按照一定的厚度将仿生空肠原材料涂抹在空肠模具与人体空肠解剖模型相接触的一面上并静置，使仿生空肠原材料凝固成型，拔出针状物且脱去模具，得到具有小肠绒毛且为中空的仿生空肠；其中，制备具有真实空肠内部生理结构且保留有针状物的空肠模具，是将可塑性材料放入并充满医学消化科精准人体空肠解剖模型，然后取下人体空肠解剖模型，再在可塑性材料的每一个与人体空肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞，最后将针状物继续保留在可塑性材料上并对可塑性材料进行固化成型，得到具有真实空肠内部生理结构且保留有针状物的空肠模具；所述仿生空肠材料是按照一定的质量比将制作仿生空肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的；
    或所述消化道为空肠时，仿生空肠的制备方法为先制备具有真实空肠内部生理结构且保留有针状物的空肠模具，然后按照一定的厚度将仿生空肠原材料涂抹在空肠模具与人体空肠解剖模型相接触的一面上并静置，使仿生空肠原材料凝固成型，拔出针状物但不脱去模具，得到具有小肠绒毛且为中空的仿生空肠，再在仿生空肠不与空肠模具相接触的那一面上覆盖一层隔离物，按照一定的厚度将仿生空肠原材料涂抹在隔离物不与仿生空肠相接触的那一面上并静置，使涂抹在隔离物表面的仿生空肠原材料凝固成型，去除隔离物并脱去模具，得到具有空肠生理结构绒毛，且可分泌肠液的仿生空肠；其中，制备具有真实空肠内部生理结构且保留有针状物的空肠模具，是将可塑性材料放入并充满医学消化科精准人体空肠解剖模型， 然后取下人体空肠解剖模型，再在可塑性材料的每一个与人体空肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞，最后将针状物继续保留在可塑性材料上并对可塑性材料进行固化成型，得到具有真实空肠内部生理结构且保留有针状物的空肠模具；所述仿生空肠材料是按照一定的质量比将制作仿生空肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的。
  6. 一种仿生胃的制备方法，其特征在于，所述方法为先制备具有真实胃底、胃体以及胃窦内部生理结构的胃底、胃体以及胃窦模具，然后按照一定的厚度将仿生胃原材料涂抹在胃底、胃体以及胃窦模具的表面并静置，使仿生胃原材料凝固成型，脱去模具，得到仿生胃；其中，制备具有真实胃底、胃体以及胃窦内部生理结构的胃底、胃体以及胃窦模具，是将可塑性材料分别放入并充满医学消化科精准人体胃解剖模型的胃底、胃体以及胃窦，然后取下医学消化科精准人体胃解剖模型并对可塑性材料进行固化成型，得到具有真实胃底、胃体以及胃窦内部生理结构的胃底、胃体以及胃窦模具；所述仿生胃材料是按照一定的质量比将制作仿生胃的基材和辅材进行混合后放入真空机中抽真空排泡得到的；所述基材包含硅胶、乳胶或水凝胶中的一种或多种；所述辅材包含硅油以及固化剂。
  7. 应用权利要求6所述的方法制备得到的仿生胃。
  8. 一种仿生大肠的制备方法，其特征在于，所述方法为先制备具有真实大肠内部生理结构的大肠模具，然后按照一定的厚度将仿生大肠原材料涂抹在大肠模具的表面并静置，使仿生大肠原材料凝固成型，脱去模具，得到仿生大肠；其中，制备具有真实大肠内部生理结构的大肠模具，是将可塑性材料放入并充满医学消化科精准人体肠道解剖模型大肠，然后取下医学消化科精准人体肠道解剖模型大肠并对可塑性材料进行固化成型，得到具有真实大肠内部生理结构的大肠模具；所述仿生大肠材料是按照一定的质量比将制作仿生大肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的；所述基材包含硅胶、乳胶或水凝胶中的一种或多种；所述辅材包含硅油以及固化剂。
  9. 应用权利要求8所述的方法制备得到的仿生大肠。
  10. 一种仿生回肠的制备方法，其特征在于，所述方法为先制备具有真实回肠内部生理结构且保留有针状物的回肠模具，然后按照一定的厚度将仿生回肠原材料涂抹在回肠模具与人体回肠解剖模型相接触的一面上并静置，使仿生回肠原材料凝固成型，拔出针状物且脱去模具，得到具有小肠绒毛且为中空的仿生回肠；其中，制备具有真实回肠内部生理结构且保留有针状物的回肠模具，是将可塑性材料放入并充满医学消化科精准人体回肠解剖模型，然后取下人体回肠解剖模型，再在可塑性材料的每一个与人体回肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞，最后将针状物继续保留在可塑性材料上并对可塑性材料进行固化 成型，得到具有真实回肠内部生理结构且保留有针状物的回肠模具；所述仿生回肠材料是按照一定的质量比将制作仿生回肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的；
    或所述方法为先制备具有真实回肠内部生理结构且保留有针状物的回肠模具，然后按照一定的厚度将仿生回肠原材料涂抹在回肠模具与人体回肠解剖模型相接触的一面上并静置，使仿生回肠原材料凝固成型，拔出针状物但不脱去模具，得到具有小肠绒毛且为中空的仿生回肠，再在仿生回肠不与回肠模具相接触的那一面上覆盖一层隔离物，按照一定的厚度将仿生回肠原材料涂抹在隔离物不与仿生回肠相接触的那一面上并静置，使涂抹在隔离物表面的仿生回肠原材料凝固成型，去除隔离物并脱去模具，得到具有回肠生理结构绒毛，且可分泌肠液的仿生回肠；其中，制备具有真实回肠内部生理结构且保留有针状物的回肠模具，是将可塑性材料放入并充满医学消化科精准人体回肠解剖模型，然后取下人体回肠解剖模型，再在可塑性材料的每一个与人体回肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞，最后将针状物继续保留在可塑性材料上并对可塑性材料进行固化成型，得到具有真实回肠内部生理结构且保留有针状物的回肠模具；所述仿生回肠材料是按照一定的质量比将制作仿生回肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的；
    所述基材包含硅胶、乳胶或水凝胶中的一种或多种；所述辅材包含硅油和/或固化剂。
  11. 应用权利要求10所述的方法制备得到的仿生回肠。
  12. 一种仿生十二指肠的制备方法，其特征在于，所述方法为先制备具有真实十二指肠内部生理结构且保留有针状物的回肠模具，然后按照一定的厚度将仿生十二指肠原材料涂抹在十二指肠模具与人体十二指肠解剖模型相接触的一面上并静置，使仿生十二指肠原材料凝固成型，拔出针状物且脱去模具，得到具有小肠绒毛且为中空的仿生十二指肠；其中，制备具有真实十二指肠内部生理结构且保留有针状物的十二指肠模具，是将可塑性材料放入并充满医学消化科精准人体十二指肠解剖模型，然后取下人体十二指肠解剖模型，再在可塑性材料的每一个与人体十二指肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞，最后将针状物继续保留在可塑性材料上并对可塑性材料进行固化成型，得到具有真实十二指肠内部生理结构且保留有针状物的十二指肠模具；所述仿生十二指肠材料是按照一定的质量比将制作仿生十二指肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的；
    或所述方法为先制备具有真实十二指肠内部生理结构且保留有针状物的回肠模具，然后按照一定的厚度将仿生十二指肠原材料涂抹在十二指肠模具与人体十二指肠解剖模型相接触的一面上并静置，使仿生十二指肠原材料凝固成型，拔出针状物但不脱去模具，得到具有小肠绒毛且为中空的仿生十二指肠，再在仿生十二指肠不与十二指肠模具相接触的那一面上覆盖一层隔离物，按照一定的厚度将仿生十二指肠原材料涂抹在隔离物不与仿生十二指肠相接 触的那一面上并静置，使涂抹在隔离物表面的仿生十二指肠原材料凝固成型，去除隔离物并脱去模具，得到具有十二指肠生理结构绒毛，且可分泌肠液的仿生十二指肠；其中，制备具有真实十二指肠内部生理结构且保留有针状物的十二指肠模具，是将可塑性材料放入并充满医学消化科精准人体十二指肠解剖模型，然后取下人体十二指肠解剖模型，再在可塑性材料的每一个与人体十二指肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞，最后将针状物继续保留在可塑性材料上并对可塑性材料进行固化成型，得到具有真实十二指肠内部生理结构且保留有针状物的回肠模具；所述仿生十二指肠材料是按照一定的质量比将制作仿生十二指肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的；
    所述基材包含硅胶、乳胶或水凝胶中的一种或多种；所述辅材包含硅油和/或固化剂。
  13. 应用权利要求12所述的方法制备得到的仿生十二指肠。
  14. 一种仿生空肠的制备方法，其特征在于，所述方法为先制备具有真实空肠内部生理结构且保留有针状物的空肠模具，然后按照一定的厚度将仿生空肠原材料涂抹在空肠模具与人体空肠解剖模型相接触的一面上并静置，使仿生空肠原材料凝固成型，拔出针状物且脱去模具，得到具有小肠绒毛且为中空的仿生空肠；其中，制备具有真实空肠内部生理结构且保留有针状物的空肠模具，是将可塑性材料放入并充满医学消化科精准人体空肠解剖模型，然后取下人体空肠解剖模型，再在可塑性材料的每一个与人体空肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞，最后将针状物继续保留在可塑性材料上并对可塑性材料进行固化成型，得到具有真实空肠内部生理结构且保留有针状物的空肠模具；所述仿生空肠材料是按照一定的质量比将制作仿生空肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的；
    或所述方法为先制备具有真实空肠内部生理结构且保留有针状物的空肠模具，然后按照一定的厚度将仿生空肠原材料涂抹在空肠模具与人体空肠解剖模型相接触的一面上并静置，使仿生空肠原材料凝固成型，拔出针状物但不脱去模具，得到具有小肠绒毛且为中空的仿生空肠，再在仿生空肠不与空肠模具相接触的那一面上覆盖一层隔离物，按照一定的厚度将仿生空肠原材料涂抹在隔离物不与仿生空肠相接触的那一面上并静置，使涂抹在隔离物表面的仿生空肠原材料凝固成型，去除隔离物并脱去模具，得到具有空肠生理结构绒毛，且可分泌肠液的仿生空肠；其中，制备具有真实空肠内部生理结构且保留有针状物的空肠模具，是将可塑性材料放入并充满医学消化科精准人体空肠解剖模型，然后取下人体空肠解剖模型，再在可塑性材料的每一个与人体空肠解剖模型上小肠绒毛相对应的凹陷处用针状物戳出小洞，最后将针状物继续保留在可塑性材料上并对可塑性材料进行固化成型，得到具有真实空肠内部生理结构且保留有针状物的空肠模具；所述仿生空肠材料是按照一定的质量比将制作仿生空肠的基材和辅材进行混合后放入真空机中抽真空排泡得到的；
    所述基材包含硅胶、乳胶或水凝胶中的一种或多种；所述辅材包含硅油和/或固化剂。
  15. 应用权利要求14所述的方法制备得到的仿生空肠。
  16. 一种仿生材料，其特征在于，所述仿生材料的成分包含基材和辅材；所述基材包含硅胶、乳胶或水凝胶中的一种或多种；所述辅材包含硅油以及固化剂。
  17. 如权利要求16所述的一种仿生材料，其特征在于，所述基材、硅油以及固化剂之间的质量比为100:(0.5～10):(0.5～3.5)。
  18. 权利要求1-5任一所述的仿生消化道或权利要求6所述的制备方法或权利要求7所述的仿生胃或权利要求8所述的制备方法或权利要求9所述的仿生大肠或权利要求10所述的制备方法或权利要求11所述的仿生回肠或权利要求12所述的制备方法或权利要求13所述的仿生十二指肠或权利要求14所述的制备方法或权利要求15所述的仿生空肠或权利要求16或17所述的仿生材料在模拟人体实际消化系统中的应用。
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