CN111136929A - Artificial bionic intestinal tract and manufacturing method thereof - Google Patents
Artificial bionic intestinal tract and manufacturing method thereof Download PDFInfo
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- CN111136929A CN111136929A CN202010094305.9A CN202010094305A CN111136929A CN 111136929 A CN111136929 A CN 111136929A CN 202010094305 A CN202010094305 A CN 202010094305A CN 111136929 A CN111136929 A CN 111136929A
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- 239000011664 nicotinic acid Substances 0.000 title claims abstract description 74
- 210000001035 gastrointestinal tract Anatomy 0.000 title claims abstract description 62
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 22
- 239000000758 substrate Substances 0.000 claims abstract description 79
- 229920002379 silicone rubber Polymers 0.000 claims abstract description 72
- 239000012528 membrane Substances 0.000 claims abstract description 64
- 238000000926 separation method Methods 0.000 claims abstract description 60
- 230000000968 intestinal effect Effects 0.000 claims abstract description 46
- 229910021426 porous silicon Inorganic materials 0.000 claims abstract description 43
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 40
- 239000000741 silica gel Substances 0.000 claims abstract description 32
- 229910002027 silica gel Inorganic materials 0.000 claims abstract description 32
- 239000002994 raw material Substances 0.000 claims abstract description 21
- 238000002360 preparation method Methods 0.000 claims abstract description 16
- 239000004721 Polyphenylene oxide Substances 0.000 claims abstract description 15
- 229920000570 polyether Polymers 0.000 claims abstract description 15
- 239000000126 substance Substances 0.000 claims abstract description 14
- 229920002545 silicone oil Polymers 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 17
- 229920006217 cellulose acetate butyrate Polymers 0.000 claims description 16
- 239000000839 emulsion Substances 0.000 claims description 16
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- 239000002131 composite material Substances 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 239000006229 carbon black Substances 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 8
- 238000000151 deposition Methods 0.000 claims description 8
- 229910052697 platinum Inorganic materials 0.000 claims description 8
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 8
- 229920002554 vinyl polymer Polymers 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 230000003592 biomimetic effect Effects 0.000 claims description 6
- 238000004090 dissolution Methods 0.000 claims description 6
- 239000011148 porous material Substances 0.000 claims description 6
- 239000004945 silicone rubber Substances 0.000 claims description 4
- 235000015097 nutrients Nutrition 0.000 abstract description 18
- 230000000694 effects Effects 0.000 abstract description 8
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- 238000006243 chemical reaction Methods 0.000 abstract description 3
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- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 abstract 1
- 229910052710 silicon Inorganic materials 0.000 abstract 1
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- 239000003513 alkali Substances 0.000 description 6
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- 210000000813 small intestine Anatomy 0.000 description 6
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- 239000001913 cellulose Substances 0.000 description 5
- 239000003995 emulsifying agent Substances 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
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- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000004913 chyme Anatomy 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
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- 239000000017 hydrogel Substances 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 210000001819 pancreatic juice Anatomy 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 230000008855 peristalsis Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
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- 238000012827 research and development Methods 0.000 description 1
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- 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
- B29C69/00—Combinations of shaping techniques not provided for in a single one of main groups B29C39/00 - B29C67/00, e.g. associations of moulding and joining techniques; Apparatus therefore
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- 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
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Abstract
The invention provides an artificial bionic intestinal canal and a manufacturing method thereof, wherein the artificial bionic intestinal canal comprises a porous silicon rubber substrate and a porous separation membrane, the inner wall of the porous silicon rubber substrate comprises fine bulges which are uniformly distributed so as to improve the specific surface area of the inner wall, and the porous separation membrane is used for separating micromolecular nutrients. The preparation method of the artificial bionic intestinal canal comprises the following steps: firstly, preparing a tubular mold, then injecting a silica gel raw material, curing and forming, then forming holes to obtain a porous silicon rubber substrate, etching the inner wall of the porous silicon rubber substrate, and preparing a layer of polyether block silicon oil porous separation membrane to obtain the artificial bionic intestinal tract. The core mold of the mold comprises fine bulges which are uniformly distributed, so that the inner wall of the bionic intestinal canal forms the fine bulges; forming holes on the surface of the silicon rubber substrate, so that the micromolecular nutrient substances can be separated from the separation membrane; the inner wall of the silicon rubber substrate is etched, so that the reaction activity of the silicon rubber substrate is improved, and the bonding fastness of the porous separation membrane and the silicon rubber substrate is further improved.
Description
Technical Field
The invention belongs to the technical field of bionics and the technical field of biology, and relates to an artificial bionic intestinal tract and a manufacturing method thereof.
Background
In the research process of food and medicine, the objective and accurate assessment of the digestion process of food and medicine in human body is important for determining the food components, medicine components and their effects on the digestive tract of human body.
The human digestive tract in-vitro bionic digestive system (such as SHIME, IViDiS, TIM, DGM, HGS and the like) is used for carrying out bionic simulation on the human digestive system, the digestive environment of the human digestive system and the dynamic behavior of fluid in the digestive tract, and can simulate the digestive processes of different samples in an in-vitro model and the influence of the samples on intestinal microorganisms, so that a large amount of valuable data are provided for the research and development of novel functional food, and if the in-vitro bionic digestive system is used as a 'pretest' to predict a living test, the in-vitro bionic digestive system can completely replace or partially replace the living test, the purposes of reducing cost and time and improving repeatability and accuracy can be achieved, and the ethical limitation is avoided.
The in vitro bionic intestinal systems commonly used in the market at present are mainly divided into two types: firstly, the stomach contents are driven to be mixed by simple containers such as beakers and the like through a stirring instrument or shaking table shaking equipment, the method is simple, convenient and cheap, and the driving (rotating speed) is controllable, but the method lacks effective simulation on the physiological form of the stomach or the intestinal tract, the physicochemical environment of the stomach or the intestine, the motion of the stomach wall or the intestinal wall and the hydrodynamic behavior; the second is a bionic digestive system with a flexible intestinal tract module and a certain peristalsis performance, which has more complex physiological morphological characteristics of the stomach and the intestinal tract, mobility of the stomach wall and the intestinal wall, continuous secretion and evacuation of gastric juice, intestinal juice and chyme, and the like, and is closer to a dynamic in-vitro bionic digestive system of the real stomach and the intestinal tract, thus becoming a main research object of researchers in recent years.
The simulated digestive tract (mainly comprising stomach, small intestine and large intestine) is used as the main body of the human digestive tract in-vitro bionic intestinal system, and the simulation degree of the simulated digestive tract to the human digestive system is important in the simulation performance of the whole human digestive tract in-vitro bionic intestinal system. The digestion and absorption processes of food in the human body are mainly completed in the stomach and the small intestine, especially the duodenum, receives both gastric juice and pancreatic juice and bile, so the digestive function of the duodenum is very important. Therefore, the simulation degree of the bionic duodenum is important for the simulation performance of the in vitro bionic intestinal system. The Chinese patent with the application number of 201811143735.4 discloses a bionic duodenum and a preparation method thereof, and the bionic duodenum is prepared by mixing a base material (one or more of silica gel, latex or hydrogel) and an auxiliary material (silicone oil and/or a curing agent) according to a certain mass ratio and smearing the mixture in a precise human intestinal anatomical model duodenum of a medical digestive department. The bionic duodenum is internally provided with annular folds, so that the surface area in the duodenum can be increased, and the microbial flora in the duodenum can better digest and absorb food; meanwhile, the small intestine villi are arranged inside the duodenum and have a hollow structure, so that intestinal juice can be secreted, and the digestion and absorption functions in the duodenum are greatly reproduced. However, the bionic duodenum does not have the function of absorbing nutrient substances after the duodenum digests food, so that intermediates and products are accumulated in the reactor, digestive enzymes are inhibited, and the simulation degree of the whole bionic intestinal system is reduced; and the bionic duodenum is obtained by smearing silica gel with a certain thickness on the surface of a mould and solidifying, and the smearing uniformity is difficult to control.
Therefore, innovative upgrading of the bionic digestive tract is urgently needed to improve the simulation performance of the bionic digestive tract, improve the digestive environment (inviscid, insoluble in water, non-reactive with acid and alkali, and resistant to high and low temperatures) of the simulated real human digestive tract, and improve the authenticity of the functions of all parts of the digestive tract.
Disclosure of Invention
In view of the above-mentioned drawbacks of the prior art, an object of the present invention is to provide an artificial bionic intestinal tract, which comprises a porous silicon rubber substrate and a porous separation membrane, wherein the porous silicon rubber substrate provides the bionic intestinal tract with good elasticity, biocompatibility, acid and alkali resistance and transparent visibility, and the inner wall comprises fine protrusions uniformly distributed, so as to increase the specific surface area of the inner wall; the porous separation membrane can separate small molecular nutrients generated by intestinal digestion, and the simulation degree is prevented from being reduced due to the accumulation of the nutrients.
The invention also aims to provide a manufacturing method of the artificial bionic intestinal canal, which comprises the steps of firstly preparing a tubular mold, then injecting a silica gel raw material, forming holes after curing and forming to obtain a porous silicon rubber substrate, and preparing a layer of porous separation membrane after etching the inner wall of the porous silicon rubber substrate to obtain the artificial bionic intestinal canal. The core mold of the mold comprises fine bulges which are uniformly distributed, so that the inner wall of the bionic intestinal canal forms the fine bulges; forming holes on the surface of the silicon rubber substrate, so that the micromolecular nutrient substances can be separated from the separation membrane; the inner wall of the silicon rubber substrate is etched, so that the reaction activity of the silicon rubber substrate is improved, and the bonding fastness of the porous separation membrane and the silicon rubber substrate is further improved.
In order to achieve the purpose, the invention adopts the following technical scheme:
an artificial bionic intestinal canal, which comprises a porous silicon rubber substrate and a porous separation membrane from outside to inside; the aperture of the porous silicon rubber substrate is 0.5-500 mu m, and the aperture of the porous separation membrane is 10-500 nm and is used for separating small molecular substances.
Further, the inner wall of the porous silicon rubber substrate comprises fine protrusions which are uniformly distributed.
Further, the thickness of the porous separation membrane is 1-200 μm.
Furthermore, the diameter of the fine bulge is 0.2-1 mm, and the height of the fine bulge is 0.5-2 mm.
The manufacturing method of the artificial bionic intestinal canal comprises the following steps:
s1, manufacturing a tubular human intestinal tract mold according to a precise human intestinal tract anatomical model of a medical gastroenterology department, wherein the mold comprises a core mold and a sleeve to form an internal cavity;
s2, injecting the uniformly mixed silica gel raw material into the inner cavity of the mold in the step S1, taking out after curing and forming, and uniformly forming holes on the surface of the silica gel raw material to obtain a porous silicon rubber substrate with the aperture of 0.5-500 mu m;
s3, preparing a porous separation membrane with the aperture of 10-500 nm on the inner wall of the porous silicon rubber substrate in the step S2 to obtain the artificial bionic intestinal tract.
Further, in step S1, the surface of the core mold includes fine protrusions uniformly distributed, and the protrusions have a diameter of 0.2 to 1mm and a height of 0.5 to 2 mm.
Further, in step S2, the silica gel raw material includes, by mass, 100 parts of vinyl silicone oil, 1 to 3 parts of hydrogen-containing silicone oil, 5 to 20 parts of white carbon black, and 0.01 to 0.05 part of platinum catalyst.
Further, in step S3, etching the inner wall of the porous silicon rubber substrate to form active hydroxyl and carboxyl on the inner wall, and then preparing a porous separation membrane with a pore size of 10-500 nm on the inner wall to obtain the artificial bionic intestinal tract.
Further, in step S3, the method for preparing the porous separation membrane includes the steps of:
s301, preparing polyether block silicone oil and cellulose acetate butyrate into emulsion according to the mass ratio of (10-15) to 1;
s302, depositing the emulsion obtained in the step S301 on the inner wall of the porous silicon rubber substrate to obtain a layer of composite film;
s303, removing the cellulose acetate butyrate in the composite membrane in the step S302 by adopting acetone dissolution to obtain the porous separation membrane.
Further, the polyether block silicone oil is polyether block amino silicone oil.
Further, the preparation of the emulsion is to add the polyether block silicone oil, cellulose acetate butyrate, emulsifier and other auxiliary agents into deionized water, and uniformly stir to prepare the uniform and stable emulsion.
Further, in step S2, the method for forming the holes includes uniformly pricking holes on the surface of the silicone rubber substrate with needles having a diameter of 0.5 to 500 μm.
Advantageous effects
Compared with the prior art, the artificial bionic intestinal tract and the manufacturing method thereof provided by the invention have the following beneficial effects:
(1) the artificial bionic intestinal canal provided by the invention sequentially comprises a porous silicon rubber substrate with the pore diameter of 0.5-500 mu m and a porous separation membrane with the pore diameter of 10-500 nm from outside to inside, wherein the pore diameter of the porous silicon rubber substrate is larger than that of the porous separation membrane, the porous separation membrane can separate small molecular nutrient substances generated by intestinal digestion, the simulation degree reduction caused by accumulation of the nutrient substances is prevented, and the porous structure of the silicon rubber substrate ensures that the small molecular nutrient substances separated from the porous separation membrane are smoothly discharged out of the bionic intestinal canal. The porous silicon rubber substrate endows the bionic intestinal tract with good elasticity, biocompatibility, acid and alkali resistance and transparency visibility, and the inner wall comprises uniformly distributed fine bulges, so that the specific surface area of the inner wall is improved, the effect similar to small intestine villus is realized, the peristaltic digestion of food is promoted, and the simulation degree is improved.
(2) The invention provides a method for manufacturing an artificial bionic intestinal canal, which comprises the steps of firstly preparing a tubular mold, then injecting a silica gel raw material, forming a hole after curing and forming to obtain a porous silicon rubber substrate, etching the inner wall of the porous silicon rubber substrate, and then preparing a layer of porous separation membrane to obtain the artificial bionic intestinal canal. The core mold of the mold comprises fine bulges which are uniformly distributed, so that the inner wall of the bionic intestinal canal forms the fine bulges; holes are formed on the surface of the silicon rubber substrate, so that the small molecular nutrient substances separated from the separation membrane can be discharged from the substrate; the inner wall of the silicon rubber substrate is etched, so that the reaction activity of the silicon rubber substrate is improved, the bonding fastness of the porous separation membrane and the silicon rubber substrate is further improved, and the service life of the bionic intestinal canal is prolonged.
(3) According to the invention, a tubular human intestinal tract mold is manufactured according to an accurate human intestinal tract anatomical model of a medical gastroenterology department, the mold comprises a core mold and a sleeve to form an internal cavity, and the surface of the core mold comprises fine bulges which are uniformly distributed and used for forming a bulge structure on the inner wall of a silicon rubber substrate. Compared with the prior art that a small intestine villus-like structure is formed by needle punching, the method has the advantages of simple preparation method, high structural uniformity and stability and strong repeatability, and the inner wall forms the bulge with the diameter of 0.2-1 mm and the height of 0.5-2 mm, so that the height of the bulge is not too high to influence the preparation of the porous separation membrane.
(4) According to the invention, the inner wall of the silicon rubber substrate is etched to obtain active groups such as hydroxyl, carboxyl and the like on the inner wall, so that the reactivity, the hydrophilicity and the roughness of the inner wall are improved; then preparing the polyether block silicone oil and the cellulose acetate butyrate into emulsion according to the mass ratio of (10-15): 1, wherein the polarity of the polyether block silicone oil is similar to that of the cellulose acetate butyrate, so that uniform and stable emulsion can be obtained; depositing the porous separation membrane on the inner wall of a silicon rubber substrate, and removing cellulose acetate butyrate to obtain the porous separation membrane. The polyether block silicone oil has good compatibility with the silicon rubber substrate, and the polyether chain segment and the active group on the inner wall can form a hydrogen bond effect, so that the porous separation membrane has high bonding fastness with the silicon rubber substrate, and on the other hand, the polyether block silicone oil has hydrophilicity and can improve the separation efficiency of micromolecules such as monosaccharide, amino acid and the like.
Detailed Description
The technical solutions of the embodiments of the present invention will be described clearly and completely below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments; all other embodiments, which can be derived by a person skilled in the art from the embodiments of the present invention without any inventive step, are within the scope of the present invention.
Example 1
An artificial bionic intestinal canal, which comprises a porous silicon rubber substrate with the aperture of 100 mu m and a porous separation membrane with the aperture of 50nm from outside to inside; the porous separation membrane has a thickness of 50 μm; the inner wall of the porous silicon rubber substrate comprises fine protrusions which are uniformly distributed and have the diameter of 0.5mm and the height of 1 mm. The preparation method comprises the following steps:
s1, manufacturing a tubular human intestinal tract mold according to a precise human intestinal tract anatomical model of a medical gastroenterology department, wherein the mold comprises a core mold and a sleeve to form an internal cavity, and the thickness of the internal cavity is 3 mm; the surface of the core mold comprises fine bulges which are uniformly distributed, the diameters of the bulges are 0.5mm, the heights of the bulges are 1mm, and the distance between every two bulges is 0.5 mm;
s2, weighing 100 parts of vinyl silicone oil, 1.5 parts of hydrogen-containing silicone oil, 15 parts of white carbon black, 0.02 part of Kansted platinum catalyst and 2 parts of inhibitor, fully stirring, uniformly mixing, and then vacuumizing for defoaming to obtain a silica gel raw material;
injecting the uniformly mixed silica gel raw material into the inner cavity of the die in the step S1, taking out after curing and forming at 120 ℃, and uniformly pricking holes on the surface of the silica gel substrate by using needles with the diameter of 100 mu m to obtain a porous silica gel substrate with the aperture of 100 mu m;
s3, performing plasma etching on the inner wall of the porous silicon rubber substrate to form active hydroxyl and carboxyl on the inner wall, and then preparing a cellulose porous separation membrane with the thickness of 50 microns on the inner wall to obtain the artificial bionic intestinal tract;
the preparation method of the porous separation membrane comprises the following steps:
s301, preparing polyether block silicone oil and cellulose acetate butyrate with the mass ratio of 12:1 into uniform and stable emulsion together with an emulsifier and water;
s302, depositing the emulsion obtained in the step S301 on the inner wall of the porous silicon rubber substrate to obtain a layer of composite film;
s303, removing the cellulose acetate butyrate in the composite membrane in the step S302 by adopting acetone dissolution to obtain the porous separation membrane.
Example 2
An artificial bionic intestinal canal, which comprises a porous silicon rubber substrate with the aperture of 300 mu m and a porous separation membrane with the aperture of 200nm from outside to inside; the porous separation membrane has a thickness of 100 μm; the inner wall of the porous silicon rubber substrate comprises fine protrusions which are uniformly distributed and have the diameter of 0.5mm and the height of 1 mm. The preparation method comprises the following steps:
s1, manufacturing a tubular human intestinal tract mold according to a precise human intestinal tract anatomical model of a medical gastroenterology department, wherein the mold comprises a core mold and a sleeve to form an internal cavity, and the thickness of the internal cavity is 3 mm; the surface of the core mold comprises fine bulges which are uniformly distributed, the diameters of the bulges are 0.5mm, the heights of the bulges are 1mm, and the distance between every two bulges is 0.5 mm;
s2, weighing 100 parts of vinyl silicone oil, 1 part of hydrogen-containing silicone oil, 10 parts of white carbon black, 0.01 part of Kanst platinum catalyst and 2 parts of inhibitor, fully stirring, uniformly mixing, and then vacuumizing and defoaming to obtain a silica gel raw material;
injecting the uniformly mixed silica gel raw material into the inner cavity of the die in the step S1, taking out after curing and forming at 120 ℃, and uniformly pricking holes on the surface of the silica gel substrate by using needles with the diameter of 300 mu m to obtain a porous silica gel substrate with the aperture of 300 mu m;
s3, performing alkali etching on the inner wall of the porous silicon rubber substrate to form active hydroxyl and carboxyl on the inner wall, and then forming a cellulose porous separation membrane with the thickness of 20 mu m on the inner wall to obtain the artificial bionic intestinal tract;
the preparation method of the porous separation membrane comprises the following steps:
s301, preparing polyether block silicone oil and cellulose acetate butyrate with the mass ratio of 10:1 into uniform and stable emulsion together with an emulsifier and water;
s302, depositing the emulsion obtained in the step S301 on the inner wall of the porous silicon rubber substrate to obtain a layer of composite film;
s303, removing the cellulose acetate butyrate in the composite membrane in the step S302 by adopting acetone dissolution to obtain the porous separation membrane.
Example 3
An artificial bionic intestinal canal, which comprises a porous silicon rubber substrate with the aperture of 1 mu m and a porous separation membrane with the aperture of 500nm from outside to inside; the porous separation membrane has a thickness of 200 μm; the inner wall of the porous silicon rubber substrate comprises fine bulges which are uniformly distributed and have the diameter of 1mm and the height of 2 mm. The preparation method comprises the following steps:
s1, manufacturing a tubular human intestinal tract mold according to a precise human intestinal tract anatomical model of a medical gastroenterology department, wherein the mold comprises a core mold and a sleeve to form an internal cavity, and the thickness of the internal cavity is 3 mm; the surface of the core mold comprises fine bulges which are uniformly distributed, the diameters of the bulges are 1mm, the heights of the bulges are 2mm, and the distance between every two bulges is 1 mm;
s2, weighing 100 parts of vinyl silicone oil, 3 parts of hydrogen-containing silicone oil, 20 parts of white carbon black, 0.05 part of Kanstedt platinum catalyst and 2 parts of inhibitor, fully stirring, uniformly mixing, and then vacuumizing and defoaming to obtain a silica gel raw material;
injecting the uniformly mixed silica gel raw material into the inner cavity of the die in the step S1, taking out after curing and forming at 120 ℃, and uniformly pricking holes on the surface of the silica gel substrate by using needles with the diameter of 1 mu m to obtain a porous silica gel substrate with the aperture of 1 mu m;
s3, performing alkali etching on the inner wall of the porous silicon rubber substrate to form active hydroxyl and carboxyl on the inner wall, and then preparing a layer of cellulose porous separation membrane with the thickness of 200 mu m on the inner wall to obtain the artificial bionic intestinal tract;
the preparation method of the porous separation membrane comprises the following steps:
s301, preparing polyether block silicone oil and cellulose acetate butyrate with a mass ratio of 15:1 and an emulsifier into emulsion;
s302, depositing the emulsion obtained in the step S301 on the inner wall of the porous silicon rubber substrate to obtain a layer of composite film;
s303, removing the cellulose acetate butyrate in the composite membrane in the step S302 by adopting acetone dissolution to obtain the porous separation membrane.
Example 4
Example 4 provides an artificial bionic intestine, which is different from example 1 in that step S3 is as follows:
and forming a layer of cellulose porous separation membrane with the thickness of 20 mu m on the inner wall of the porous silicon rubber substrate by adopting a dipping deposition method to obtain the artificial bionic intestinal canal.
The rest is basically the same as embodiment 1, and is not described herein again.
Comparative example 1
An artificial bionic intestinal canal, which comprises a silicon rubber substrate and a porous separation membrane with the aperture of 50nm from outside to inside; the porous separation membrane has a thickness of 50 μm; the inner wall of the silicon rubber substrate comprises fine bulges which are uniformly distributed and have the diameter of 0.5mm and the height of 1 mm. The preparation method comprises the following steps:
s1, manufacturing a tubular human intestinal tract mold according to a precise human intestinal tract anatomical model of a medical gastroenterology department, wherein the mold comprises a core mold and a sleeve to form an internal cavity, and the thickness of the internal cavity is 3 mm; the surface of the core mold comprises fine bulges which are uniformly distributed, the diameters of the bulges are 0.5mm, the heights of the bulges are 1mm, and the distance between every two bulges is 0.5 mm;
s2, weighing 100 parts of vinyl silicone oil, 1.5 parts of hydrogen-containing silicone oil, 15 parts of white carbon black, 0.02 part of Kansted platinum catalyst and 2 parts of inhibitor, fully stirring, uniformly mixing, and then vacuumizing for defoaming to obtain a silica gel raw material;
injecting the uniformly mixed silica gel raw material into the inner cavity of the mold in the step S1, curing and molding at 120 ℃, and taking out to obtain a silicone rubber substrate;
s3, performing plasma etching on the inner wall of the silicon rubber substrate to form active hydroxyl and carboxyl on the inner wall, and then preparing a cellulose porous separation membrane with the thickness of 50 microns on the inner wall to obtain the artificial bionic intestinal tract;
the preparation method of the porous separation membrane comprises the following steps:
s301, preparing polyether block silicone oil and cellulose acetate butyrate with the mass ratio of 12:1 and an emulsifier into emulsion;
s302, depositing the emulsion obtained in the step S301 on the inner wall of the porous silicon rubber substrate to obtain a layer of composite film;
s303, removing the cellulose acetate butyrate in the composite membrane in the step S302 by adopting acetone dissolution to obtain the porous separation membrane.
Comparative example 2
An artificial bionic intestinal canal is a porous silicon rubber substrate with the aperture of 100 mu m, and the inner wall of the porous silicon rubber substrate comprises fine bulges which are uniformly distributed and have the diameter of 0.5mm and the height of 1 mm. The preparation method comprises the following steps:
s1, manufacturing a tubular human intestinal tract mold according to a precise human intestinal tract anatomical model of a medical gastroenterology department, wherein the mold comprises a core mold and a sleeve to form an internal cavity, and the thickness of the internal cavity is 3 mm; the surface of the core mold comprises fine bulges which are uniformly distributed, the diameters of the bulges are 0.5mm, the heights of the bulges are 1mm, and the distance between every two bulges is 0.5 mm;
s2, weighing 100 parts of vinyl silicone oil, 1.5 parts of hydrogen-containing silicone oil, 15 parts of white carbon black, 0.02 part of Kansted platinum catalyst and 2 parts of inhibitor, fully stirring, uniformly mixing, and then vacuumizing for defoaming to obtain a silica gel raw material;
and (3) injecting the uniformly mixed silica gel raw material into the inner cavity of the die in the step S1, curing and forming at 120 ℃, taking out, and uniformly puncturing the surface of the silica gel substrate by using a needle with the diameter of 100 microns to obtain a porous silica gel substrate with the aperture of 100 microns, namely the bionic intestinal tract.
Comparative example 3
The utility model provides an artificial bionic intestinal, artificial bionic intestinal is the silicon rubber basement, the inner wall of silicon rubber basement contains evenly distributed's diameter and is 0.5mm, highly is 1 mm's tiny arch. The preparation method comprises the following steps:
s1, manufacturing a tubular human intestinal tract mold according to a precise human intestinal tract anatomical model of a medical gastroenterology department, wherein the mold comprises a core mold and a sleeve to form an internal cavity, and the thickness of the internal cavity is 3 mm; the surface of the core mold comprises fine bulges which are uniformly distributed, the diameters of the bulges are 0.5mm, the heights of the bulges are 1mm, and the distance between every two bulges is 0.5 mm;
s2, weighing 100 parts of vinyl silicone oil, 1.5 parts of hydrogen-containing silicone oil, 15 parts of white carbon black, 0.02 part of Kansted platinum catalyst and 2 parts of inhibitor, fully stirring, uniformly mixing, and then vacuumizing for defoaming to obtain a silica gel raw material;
and (4) injecting the uniformly mixed silica gel raw material into the inner cavity of the die in the step S1, curing and forming at 120 ℃, and taking out to obtain a silica gel substrate, namely the bionic intestinal canal.
The intestinal areas and the elasticity of the artificial biomimetic intestinal tracts manufactured in examples 1 to 4 and comparative examples 1 to 3 were examined using a method similar to that of the chinese patent application No. 201811143735.4.
The separation function of the small molecule nutrient substances is detected by the following method: fixing the artificial bionic intestinal tract at corresponding position of in vitro bionic digestive system (such as TIM and DGM), adding food and corresponding digestive juice, operating the in vitro bionic digestive system, and detecting whether discharged small molecular nutrients exist outside the bionic intestinal tract.
Results of Performance test of examples 1 to 4 and comparative examples 1 to 3
| Test specimen | Intestinal area/cm2 | Elasticity | Whether the function of separating small molecular nutrient substances is provided |
| Example 1 | ＞2000 | 750% | Is that |
| Practice ofExample 2 | ＞2000 | 720% | Is that |
| Example 3 | ＞2000 | 780% | Is that |
| Example 4 | ＞2000 | 750% | Is that |
| Comparative example 1 | ＞2000 | 750% | Whether or not |
| Comparative example 2 | ＞2000 | 750% | Is that |
| Comparative example 3 | ＞2000 | 750% | Whether or not |
As can be seen from table 1, the artificial simulated intestinal tracts manufactured in examples 1 to 4 all had the function of separating small molecular nutrients, whereas comparative examples 1 and 3 did not. Comparative example 2 although small molecular nutrients (such as monosaccharides and amino acids) can be separated, other components (such as digestive enzymes) of the digestive juice are easily discharged from the bionic intestinal tract due to the large pore size of the silicon rubber, and the digestion function is reduced.
In summary, the invention separates the micromolecular nutrient substances generated by intestinal digestion through the porous separation membrane, prevents the simulation degree from being reduced due to the accumulation of the nutrient substances, and ensures that the micromolecular nutrient substances separated from the porous separation membrane are smoothly discharged from the bionic intestinal tract through the porous structure of the silicon rubber substrate. The porous silicon rubber substrate endows the bionic intestinal tract with good elasticity, biocompatibility, acid and alkali resistance and transparency visibility, and the inner wall comprises uniformly distributed fine bulges, so that the specific surface area of the inner wall is improved, the effect similar to small intestine villus is realized, the peristaltic digestion of food is promoted, and the simulation degree is improved.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.
Claims (10)
1. An artificial bionic intestinal canal is characterized in that the artificial bionic intestinal canal comprises a porous silicon rubber substrate and a porous separation membrane from outside to inside; the aperture of the porous silicon rubber substrate is 0.5-500 mu m, and the aperture of the porous separation membrane is 10-500 nm and is used for separating small molecular substances.
2. The artificial biomimetic intestinal tract according to claim 1, wherein the inner wall of the porous silicone rubber substrate comprises fine protrusions uniformly distributed.
3. The artificial biomimetic intestinal tract according to claim 1, wherein the thickness of the porous separation membrane is 1-200 μm.
4. The artificial bionic intestinal canal as claimed in claim 2, wherein the diameter of the fine protrusion is 0.2-1 mm, and the height is 0.5-2 mm.
5. A method of manufacturing an artificial biomimetic intestinal tract according to any of claims 1-4, characterized in that it comprises the steps of:
s1, manufacturing a tubular human intestinal tract mold according to a precise human intestinal tract anatomical model of a medical gastroenterology department, wherein the mold comprises a core mold and a sleeve to form an internal cavity;
s2, injecting the uniformly mixed silica gel raw material into the inner cavity of the mold in the step S1, taking out after curing and forming, and uniformly forming holes on the surface of the silica gel raw material to obtain a porous silicon rubber substrate with the aperture of 0.5-500 mu m;
s3, preparing a porous separation membrane with the aperture of 10-500 nm on the inner wall of the porous silicon rubber substrate in the step S2 to obtain the artificial bionic intestinal tract.
6. The method for manufacturing an artificial biomimetic intestinal tract according to claim 5, wherein in step S1, the surface of the mandrel comprises fine protrusions uniformly distributed, and the protrusions have a diameter of 0.2-1 mm and a height of 0.5-2 mm.
7. The method for manufacturing an artificial bionic intestinal canal according to claim 5, wherein in step S2, the silica gel raw material comprises, by mass, 100 parts of vinyl silicone oil, 1-3 parts of hydrogen-containing silicone oil, 5-20 parts of white carbon black, and 0.01-0.05 part of platinum catalyst.
8. The method for manufacturing the artificial bionic intestinal canal according to claim 5, wherein in step S3, the inner wall of the porous silicon rubber substrate is etched to form active hydroxyl and carboxyl on the inner wall, and then a porous separation membrane with a pore diameter of 10-500 nm is prepared on the inner wall to obtain the artificial bionic intestinal canal.
9. The method for manufacturing an artificial biomimetic intestinal tract according to claim 5 or 8, wherein in step S3, the preparation method of the porous separation membrane includes the steps of:
s301, preparing polyether block silicone oil and cellulose acetate butyrate into emulsion according to the mass ratio of (10-15) to 1;
s302, depositing the emulsion obtained in the step S301 on the inner wall of the porous silicon rubber substrate to obtain a layer of composite film;
s303, removing the cellulose acetate butyrate in the composite membrane in the step S302 by adopting acetone dissolution to obtain the porous separation membrane.
10. The method for manufacturing an artificial bionic intestinal tract according to claim 5, wherein in step S2, the hole is formed by uniformly pricking holes on the surface of the silicone rubber substrate with needles with a diameter of 0.5-500 μm.
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