CN109333883B - A kind of bionic ileum and preparation method thereof - Google Patents

Abstract

The invention discloses a bionic ileum and a preparation method thereof, belonging to the field of bionic technology and the field of biotechnology. The bionic ileum of the present invention is prepared by mixing the base material (one or more of silica gel, latex or hydrogel) and auxiliary materials (silicone oil and/or curing agent) according to a certain mass ratio and then applying it to the medical gastroenterology department. Made in the ileum of the human intestinal anatomy model; the simulation performance of the bionic ileum of the present invention is superior (the Shore A hardness is 32 ± 5, the expansion rate is 28 ± 5%, and the elasticity is 220 ± 50%), and it has human The shape and physiological structure of the real ileum can truly simulate the digestive environment in the human ileum. For example, the bionic ileum has circular folds inside, which can increase the surface area of the intestine, allowing the microbial flora in the ileum to better digest and absorb food. At the same time, the bionic ileum has small intestinal villi inside, and the small intestinal villus is a hollow structure, which can secrete intestinal juice and greatly reproduce the function of digestion and absorption in the ileum.

Description

A kind of bionic ileum and preparation method thereof

technical field

The invention relates to a bionic ileum and a preparation method thereof, belonging to the field of bionic technology and the field of biotechnology.

Background technique

In the research process of food and medicine, it is very important to objectively and accurately evaluate the digestion process of food and medicine in the human body to determine the components of food and medicine and their effects on the human digestive tract.

The human digestive tract in vitro simulation device (such as SHIME, IViDiS, TIM, DGM, HGS, etc.) is a device for bionic simulation of the human digestive system, its digestive environment, and the fluid dynamic behavior in the digestive tract. It can simulate different samples in an in vitro model. The digestive process of these samples and the influence of these samples on intestinal microorganisms provide a lot of valuable data for the research and development of new functional foods. If it is used as a "pre-test" to predict the in vivo test and completely replace or partially replace the in vivo test, it can be Achieve the goal of reducing cost and time, improving repeatability and accuracy, and there is no theoretical limit.

Therefore, the human digestive tract in vitro simulation device is more and more critical in the research of food, medicine, and even microorganisms. It provides great convenience for the research of food science and human nutrition, which 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 the human digestive tract in vitro simulation device, and its degree of simulation of the real human digestive tract is very important in the simulation performance of the entire human digestive tract in vitro simulation device.

At present, people usually use silica gel, latex and other materials to make simulated digestive tract models, which can well reproduce the digestive environment in the digestive tract, such as non-viscosity, insoluble in water, non-reactive with acid and alkali, high and low temperature resistance, etc.

However, the internal physiological structures of these existing digestive tract models made of silica gel and latex are smooth and single, for example, small intestine models, and these small intestine models often have the following structural defects: one is that there is no small intestinal villi, which makes the intestines The area in contact with food is too small, resulting in limited function of digestion and absorption in the small intestine; second, the intestinal juice is expressed in the form of direct addition, and the secretion of intestinal juice is uneven, resulting in inaccurate test results.

Moreover, these digestive tract models are often simply made as a whole structure, for example, a whole stomach is molded with silicone or latex at one time, and these whole stomachs cannot simulate the "back jet" function between the gastric antrum and the gastric body, resulting in The experimental results are inaccurate.

At the same time, these digestive tract models made of silica gel and latex are actually not satisfactory in terms of simulation performance, such as hardness, expansion rate, and elasticity, and there is still a certain gap with the real human digestive tract.

Therefore, there is an urgent need to innovate and upgrade the bionic digestive tract to improve its simulation performance, improve its simulated digestive environment of the real human digestive tract (non-viscous, insoluble in water, non-reactive with acid and alkali, high and low temperature resistance) and various parts of the digestive tract authenticity of the function.

Contents of the invention

To solve the above problems, the present invention provides a bionic ileum and a preparation method thereof. This bionic ileum is made by base material (one or more in silica gel, latex or hydrogel) and auxiliary material (silicone oil and/or curing agent) according to certain mass ratio (the base material, silicone oil and curing agent The mass ratio between them is 100:2.5～3.5:0.5～1.5) mixed and applied to the ileum of the accurate human intestinal anatomy model in the department of medical gastroenterology; the simulation performance of this bionic ileum is superior (Shore A hardness is 32 ±5, the expansion rate is 28±5%, and the elasticity is 220±50%), and has the shape and physiological structure of the real human ileum, which can truly simulate the digestive environment in the human ileum. For example, the interior of this bionic ileum has a ring Wrinkles can increase the surface area of the intestine, which in turn allows the microbial flora in the ileum to better digest and absorb food. At the same time, the bionic ileum has small intestinal villi inside, and the small intestinal villus is a hollow structure that can secrete intestinal juice, greatly recreating the ileum Therefore, this bionic ileum can simulate the real functions of food, medicine, microorganisms, etc. in the ileum of the digestive system, and has great application prospects in the research process of food and medicine.

Technical scheme of the present invention is as follows:

The invention provides a method for preparing a bionic ileum. The method is to put plastic materials into an accurate human ileum anatomical model in the department of medical gastroenterology for modeling, remove the human ileum anatomical model, and place each plastic material with the human ileum On the anatomical model, use a needle to poke a small hole in the depression corresponding to the villi of the small intestine, keep the needle on the plastic material and solidify the plastic material to obtain an ileum mold with a real internal physiological structure of the ileum; according to a certain The mass ratio of the bionic ileum is mixed with the base material and auxiliary materials to obtain the bionic ileum raw material; according to a certain thickness, the bionic ileum raw material is smeared on the side of the ileum mold that is in contact with the human ileum anatomical model, and it is left to stand so that the ileum mold is applied The bionic ileum material on the surface is solidified and formed, the needle is pulled out and the ileum mold is removed to obtain a hollow bionic ileum with small intestinal villi;

Or the method is to put the plastic material into the accurate human ileum anatomical model of the medical department of gastroenterology for modeling, take off the human ileum anatomical model, and use the plastic material in each depression corresponding to the small intestinal villi on the human ileal anatomical model The needles poke out small holes, keep the needles on the plastic material and solidify the plastic material to obtain the ileum mold with the real internal physiological structure of the ileum; according to a certain mass ratio, the base material and Mix the auxiliary materials to obtain the bionic ileum raw material; apply the bionic ileum raw material on the side of the ileum mold that is in contact with the human ileum anatomical model according to a certain thickness, and let it stand to make the bionic ileum raw material coated on the surface of the ileum mold solidify and form, and only pull out A needle-shaped object to obtain a hollow bionic ileum with villi of the small intestine; a layer of spacer is covered on the side of the bionic ileum that is not in contact with the ileum mold, and the raw material of the bionic ileum is smeared on the side of the bionic ileum that is not in contact with the bionic ileum according to a certain thickness. On the side that is in contact, let it stand still to solidify the bionic ileum raw material applied on the surface of the spacer, remove the spacer and take off the ileum mold, and obtain a bionic ileum that has the villi of the ileum physiological structure and can secrete intestinal juice;

The base material includes one or more of silica gel, latex or hydrogel; the auxiliary material includes silicone oil and/or curing agent.

In one embodiment of the present invention, the accurate anatomical model of the human intestinal tract in the department of medical gastroenterology is a 1:1 hollow model of the real intestinal tract.

In one embodiment of the present invention, the plastic material comprises clay, paraffin, glass or steel.

In one embodiment of the present invention, the plastic material comprises clay, paraffin, glass or steel.

In one embodiment of the present invention, the clay is soft clay.

In one embodiment of the present invention, the method is to put soft clay into an accurate human ileum anatomical model in the department of medical gastroenterology for modeling, take off the human ileum anatomical model, and place soft clay on each of the soft clay and human ileum. Use a needle to poke a small hole in the depression corresponding to the villi of the small intestine on the anatomical model, keep the needle on the soft clay and bake the soft clay to make it solidify and cool naturally to prevent the mold from cooling down quickly Cracks are generated to obtain the ileum mold with the real internal physiological structure of the ileum; the base material and auxiliary materials for making the bionic ileum are mixed according to a certain mass ratio, and then put into a vacuum machine to evacuate and defoam to obtain the raw material of the bionic ileum; according to a certain mass ratio Apply the bionic ileum raw material on the inner side of the ileum mould, let stand to solidify the biomimetic ileum raw material smeared on the surface of the ileum mould, pull out the needle and take off the ileum mould, and obtain a hollow bionic ileum with villi of the small intestine;

Or the method is to first put the soft clay into the accurate human ileum anatomical model of the medical department of gastroenterology for modeling, take off the human ileum anatomical model, and place the soft clay on each part of the soft clay corresponding to the small intestinal villi on the human ileal anatomical model. Use needles to poke small holes in the depression, keep the needles on the soft clay and bake the soft clay to solidify and shape, and let it cool naturally to prevent cracks caused by rapid cooling of the mold, so as to obtain a real interior of the ileum Physiological structure ileum mold; according to a certain mass ratio, the base material and auxiliary materials for bionic ileum are mixed, and then put into a vacuum machine to vacuumize and defoam to obtain the bionic ileum raw material; according to a certain thickness, the bionic ileum raw material is smeared on the ileum The inner side of the mold is left to stand until the bionic ileum raw material applied on the surface of the ileum mold is solidified and formed, and only the needle is pulled out to obtain a hollow bionic ileum with small intestinal villi; the side of the bionic ileum that is not in contact with the ileum mold is covered with a Layer the spacer, apply the air-free mixed raw material on the side of the spacer that is not in contact with the bionic ileum according to a certain thickness, let it stand to make the bionic ileum raw material applied on the surface of the spacer solidify and form, remove the spacer and take off the ileum The mold was used to obtain a bionic ileum that had the villi of the physiological structure of the ileum and could secrete intestinal juice.

In one embodiment of the present invention, the baking time is 15-30 minutes.

In one embodiment of the present invention, the diameter of the small hole is 0.2-1mm

In one embodiment of the present invention, when poking a small hole in each of the soft clay clay corresponding to the small intestinal villi on the anatomical model of the human ileum, the needle should penetrate the clay clay and make the One end of the needle protrudes at least 2 mm from the side where the soft clay is in contact with the anatomical model of the human ileum.

In one embodiment of the present invention, the diameter of the ileum mold is 1.5-2.5 cm, and the length is 20-30 cm.

In one embodiment of the present invention, the mass ratio among the substrate, the silicone oil and the curing agent is 100:(2.5-3.5):(0.5-1.5).

In one embodiment of the present invention, the mass ratio between the base material and the auxiliary material is 100:3:1.

In one embodiment of the present invention, the substrate is silica gel.

In one embodiment of the present invention, the silica gel is transparent silica gel or translucent silica gel.

In one embodiment of the present invention, the curing agent comprises tetraethyl orthosilicate, vinyltriamine, DETA aminoethylpiperazine AE, m-phenylenediamine m-PDAMPD, diaminodiphenylmethane DDM or One or more of HT-972DEH-50.

In one embodiment of the present invention, the conditions for vacuuming and defoaming are vacuum machine negative pressure -0.1-0.09 MPa, time 5-10 min.

In one embodiment of the present invention, the conditions for vacuuming and defoaming are a negative pressure of 0.09 MPa in a vacuum machine and a time of 7 minutes.

In one embodiment of the present invention, the thickness of the bionic ileum raw material applied on the surface of the ileum mold is 2-3 mm.

In one embodiment of the present invention, the thickness of the bionic ileum raw material applied on the surface of the ileum mold is 2.5mm.

In one embodiment of the present invention, the standing time is 2-4 hours.

In one embodiment of the present invention, the standing time is 3 hours.

In one embodiment of the present invention, the spacer comprises oily paper or plastic wrap.

In one embodiment of the present invention, the thickness of the bionic ileum raw material applied on the surface of the separator is 2-3 mm.

In one embodiment of the present invention, the thickness of the bionic ileum raw material applied on the surface of the separator is 2.5 mm.

The invention provides a bionic ileum prepared by applying the above-mentioned bionic ileum preparation method.

The present invention provides the above-mentioned preparation method of the bionic ileum or the application of the above-mentioned prepared bionic ileum in simulating the actual digestive system of a human body.

Beneficial effect:

(1) The bionic ileum simulation performance of the present invention is superior (the Shore A hardness is 32±5, the expansion rate is 28±5%, and the elasticity is 220±50%). Simulate the digestive environment in the human ileum;

(2) The interior of the bionic ileum of the present invention has annular folds, which can increase the surface area of the intestine, thereby allowing the microbial flora in the ileum to better digest and absorb food;

(3) The bionic ileum of the present invention has small intestinal villi inside, and the small intestinal villi can be a double-layer hollow structure. If the intestinal fluid is filled into the hollow part, the small intestinal villi can automatically secrete intestinal juice during peristalsis, greatly reproducing the ileum. The function of digestion and absorption;

(4) The bionic ileum of the present invention can be dynamically transparent or translucent, and can realize real and real-time in vitro observation of the internal digestive state of the ileum;

(5) The bionic ileum of the present invention uses silica gel as the base material, which has the advantages of non-stickiness, insoluble in water, no reaction with acid and alkali, high and low temperature resistance, etc., and can well reproduce the digestion and absorption environment in the ileum;

(6) The bionic ileum of the present invention can simulate the real functions of food, medicine, microorganisms, etc. in the ileum of the digestive system, and has great application prospects in the research process of food and medicine.

Description of drawings

Figure 1: Frontal photo of the bionic ileum of the present invention;

Fig. 2: The photo of the reverse side of the bionic ileum of the present invention;

Figure 3: Photo of the small intestinal villi of the bionic ileum of the present invention;

Figure 4: Photograph of the small intestinal villi of the bionic ileum of the present invention.

Detailed ways

The present invention will be further elaborated below in conjunction with specific examples.

The detection methods involved in the following examples are as follows:

Intestinal area detection method:

S＝2πr ₁ h ₁ +n(π-1)r ₂ h ₂ ;

Among them, S is the area of the intestine, _r1 is the radius of the intestine, _h1 is the height of the intestine, n is the number of the intestinal wall, _r2 is the radius of the intestinal wall, and _h2 is the height of the intestinal wall.

Transparency detection method:

Use visual inspection to observe whether the silica gel is transparent, translucent, and has air bubbles, and stretch the silica gel to see if it is whitish. The whitish is opaque. Put rice, corn and other food into the silica gel to see if it can be clearly seen The appearance of the food.

If the surface of the food can be clearly seen, the transparency is good; if the outline of the food can be seen, the transparency is moderate; if the image of the food cannot be seen, the transparency is poor.

Hardness (Shore hardness) detection method:

The Shore hardness tester is used for measurement, and the indenter of the hardness tester is pressed on the surface of the stomach to measure the depth of the indenter into the surface of the stomach.

Expansion rate detection method:

Pe=(W*m/A)×100%;

Among them, Pe is the expansion rate, W is the total balance load, A is the area of the silica gel, and m is the lever ratio of the pressurized equipment.

Elasticity detection method:

Perform a tensile test on the silica gel on a tensile testing machine to measure the axial elongation and transverse elongation of the silica gel until the silica gel breaks.

C=(D-d)×100%/d;

Among them, C is the modulus of elasticity, D is the elongation, and d is the initial length of silica gel.

Functional test of intestinal juice secreted by villi:

The obtained bionic duodenum is fixed in the intestinal visualization bionic reactor through the flange interface of the pipeline (for the intestinal visualization bionic reactor, please refer to the invention patent with publication number CN108318625A), add 100ml of pancreatic juice to the silicone bionic duodenum During the process, the reactor was run for 10 minutes, and the volume of secreted pancreatic juice was observed.

Example 1: Preparation of bionic ileum

(1) Prepare clay: knead the soft clay repeatedly to obtain soft clay with good ductility;

(2) Ileum mold pressing: Put the kneaded soft clay into the precise human ileum anatomical model of the medical gastroenterology department, squeeze it hard, remove the human ileum anatomical model, and obtain the soft clay ileum with the real internal physiological structure of the ileum Mold, the diameter of the mold is 1.5cm, and the length is 25cm;

(3) Production of hollow fluff: Take a number of needles with a diameter of 0.5mm, stick them on each imprint on the above mold, poke a small hole with a diameter of 1mm and a depth of 5mm, and the needles will continue to remain inside the mold

(4) Bake molding of the ileum mold: put the ileum mold into an oven and bake at 140°C for 15 minutes to solidify the ileum mold and cool naturally to obtain a bionic ileum mold;

(8) Prepare silica gel: put transparent silica gel, silicone oil and curing agent ethyl orthosilicate in a ratio of 100:3:1 in a beaker, stir well, and mix well;

(9) Put the uniformly mixed silica gel into a vacuum machine, under a negative pressure of 0.09MPa, vacuumize and debubble for 5 minutes, and obtain a bubble-free silica gel;

(10) Apply bubble-free silica gel evenly on the surface of the bionic ileum mold obtained above, with a thickness of about 2 mm;

(11) Leave the evenly smeared ileum mold for 2 hours to make it completely solidified and formed, then pull out the needle outside the mold to obtain a hollow ileum silica gel model with small intestinal villi;

(12) Cover the surface of the above-mentioned ileum mold with only the needle removed and the silica gel that has not fallen off with a piece of oily paper, and place a hollow cylinder with a diameter of 2 cm and a height of 4 cm on the outside, and fix it;

(13) Evenly apply bubble-free silica gel to the gap between the oily paper of the ileum mold and the cylinder, and let it stand for 2 hours until it is completely solidified and formed;

(14) Place the solidified silicone mold in water for 10 minutes, and after the water softens the oily paper, take the oily paper out of the hollow cylinder;

(15) After the silica gel is removed from the ileum mold, and then after a certain trimming process, a bionic ileum silica gel model with the physiological structure of the ileum, intestinal wall folds and villi, and the villi can secrete intestinal juice can be obtained.

Example 2: Preparation of bionic ileum

(1) Prepare clay: knead the soft clay repeatedly to obtain soft clay with good ductility;

(2) Ileum mold pressing: Put the kneaded soft clay into the precise human ileum anatomical model of the medical gastroenterology department, squeeze it hard, remove the human ileum anatomical model, and obtain the soft clay ileum with the real internal physiological structure of the ileum Mold, the diameter of the mold is 2cm, and the length is 25cm;

(3) Production of hollow fluff: Take a number of needles with a diameter of 0.3mm, stick them on each mark on the above mold, poke a small hole with a diameter of 0.5mm and a depth of 5mm, and the needles will continue to remain inside the mold

(4) Bake molding of the ileum mold: put the ileum mold into an oven and bake at 150°C for 20 minutes to solidify the ileum mold and cool naturally to obtain a bionic ileum mold;

(8) Prepare silica gel: put transparent silica gel, silicone oil and curing agent vinyltriamine in a ratio of 100:3:1.5 into a beaker, stir well, and mix well;

(9) Put the uniformly mixed silica gel into a vacuum machine, under a negative pressure of 0.09MPa, vacuumize and debubble for 5 minutes, and obtain a bubble-free silica gel;

(10) Apply bubble-free silica gel evenly on the surface of the bionic ileum mold obtained above, with a thickness of about 2.5mm;

(11) Leave the uniformly smeared ileum mold for 4 hours to make it completely solidified and formed, then pull out the needle outside the mold to obtain a hollow ileum silica gel model with small intestinal villi;

(12) Cover the surface of the above-mentioned ileum mold with only the needle removed and the silica gel that has not fallen off with a piece of oily paper, and place a hollow cylinder with a diameter of 2 cm and a height of 4 cm on the outside, and fix it;

(13) Evenly apply bubble-free silica gel to the gap between the oily paper of the ileum mold and the cylinder, and let it stand for 1 hour until it is completely solidified and formed;

(14) Place the solidified silicone mold in water for 10 minutes, and after the water softens the oily paper, take the oily paper out of the hollow cylinder;

(15) After the silica gel is removed from the ileum mold, and then after a certain trimming process, a bionic ileum silica gel model with the physiological structure of the ileum, intestinal wall folds and villi, and the villi can secrete intestinal juice can be obtained.

Example 3: Preparation of bionic ileum

(1) Prepare clay: knead the soft clay repeatedly to obtain soft clay with good ductility;

(2) Ileum mold pressing: put the kneaded soft clay into the precise human ileum anatomical model of the medical gastroenterology department, squeeze it hard, remove the human ileum anatomical model, and obtain the soft clay ileum with the real internal physiological structure of the ileum Mold, the diameter of the mold is 2.5cm, and the length is 30cm;

(3) Production of hollow fluff: Take a number of needles with a diameter of 0.1mm, stick them on each mark on the above mold, poke a small hole with a diameter of 0.2mm and a depth of 5mm, and the needles will continue to remain inside the mold

(4) Bake molding of the ileum mold: Put the ileum mold into an oven and bake at 130°C for 30 minutes to solidify the ileum mold and cool naturally to obtain a bionic ileum mold;

(8) Prepare silica gel: put transparent silica gel, silicone oil and curing agent diaminodiphenylmethane DDM in a ratio of 100:2.5:1 into a beaker, stir well, and mix well;

(9) Put the uniformly mixed silica gel into a vacuum machine, under a negative pressure of 0.09MPa, vacuumize and debubble for 5 minutes, and obtain a bubble-free silica gel;

(10) Apply bubble-free silica gel evenly on the surface of the bionic ileum mold obtained above, with a thickness of about 3mm;

(11) Leave the evenly smeared ileum mold for 1 hour to make it completely solidified and formed, then pull out the needle outside the mold to obtain a hollow ileum silicone model with small intestinal villi;

(12) Cover the surface of the above-mentioned ileum mold with only the needle removed and the silica gel that has not fallen off with a piece of oily paper, and place a hollow cylinder with a diameter of 2 cm and a height of 4 cm on the outside, and fix it;

(13) Evenly apply bubble-free silica gel to the gap between the oily paper of the ileum mold and the cylinder, and let it stand for 1 hour until it is completely solidified and formed;

(14) Place the solidified silicone mold in water for 10 minutes, and after the water softens the oily paper, take the oily paper out of the hollow cylinder;

(15) After the silica gel is removed from the ileum mold, and then after a certain trimming process, a bionic ileum silica gel model with the physiological structure of the ileum, intestinal wall folds and villi, and the villi can secrete intestinal juice can be obtained.

Comparative Example 1: Preparation of bionic ileum (without villi)

(1) Prepare clay: knead the soft clay repeatedly to obtain soft clay with good ductility;

(2) Ileum mold pressing: Put the kneaded soft clay into the precise human ileum anatomical model of the medical gastroenterology department, squeeze it hard, remove the human ileum anatomical model, and obtain the soft clay ileum with the real internal physiological structure of the ileum Mold, the diameter of the mold is 2.5cm, and the length is 30cm;

(4) Bake molding of the ileum mold: Put the ileum mold into an oven and bake at 130°C for 30 minutes to solidify the ileum mold and cool naturally to obtain a bionic ileum mold;

(8) Prepare silica gel: put transparent silica gel, silicone oil and curing agent ethyl orthosilicate in the ratio of 100:3.5:0.5 into a beaker, stir well, and mix well;

(9) Put the uniformly mixed silica gel into a vacuum machine, under a negative pressure of 0.09MPa, vacuumize and debubble for 5 minutes, and obtain a bubble-free silica gel;

(10) Apply bubble-free silica gel evenly on the surface of the bionic ileum mold obtained above, with a thickness of about 2.5mm;

(11) Leave the ileum mold that is evenly applied for 1 hour to make it completely solidify and form;

(15) After the silica gel is removed from the ileum mold, a bionic ileum silica gel model with folds of the intestinal wall of the ileum physiological structure can be obtained after a certain trimming process.

Comparative example 2: Preparation of bionic ileum (silica gel is not evacuated after mixing)

(1) Prepare clay: knead the soft clay repeatedly to obtain soft clay with good ductility;

(2) Ileum mold pressing: put the kneaded soft clay into the precise human ileum anatomical model of the medical gastroenterology department, squeeze it hard, remove the human ileum anatomical model, and obtain the soft clay ileum with the real internal physiological structure of the ileum Mold, the diameter of the mold is 2cm, and the length is 30cm;

(3) Production of hollow fluff: Take a number of needles with a diameter of 0.2mm, stick them on each imprint on the above mold, poke a small hole with a diameter of 0.5mm and a depth of 5mm, and the needles will continue to remain inside the mold

(4) Bake molding of the ileum mold: put the ileum mold into an oven and bake at 140°C for 20 minutes to solidify the ileum mold and cool naturally to obtain a bionic ileum mold;

(8) Prepare silica gel: put transparent silica gel, silicone oil and curing agent ethyl orthosilicate in a ratio of 100:3:0.5 in a beaker, stir well, and mix evenly;

(9) Evenly smear silica gel on the surface of the bionic ileum mold obtained above, with a thickness of about 2.5 mm;

(10) Leave the uniformly smeared ileum mold for 2 hours to make it completely solidified and formed, then pull out the needle outside the mold to obtain a hollow ileum silica gel model with small intestinal villi;

(11) Cover the surface of the above-mentioned ileum mold with only the needle removed and the silica gel that has not fallen off with a piece of oily paper, and place a hollow cylinder with a diameter of 2 cm and a height of 4 cm on the outside, and fix it;

(12) Evenly apply bubble-free silica gel to the gap between the oily paper of the ileum mold and the cylinder, and let it stand for 2 hours until it is completely solidified and formed;

(13) Place the solidified silicone mold in water for 10 minutes, and after the water softens the oily paper, take the oily paper out of the hollow cylinder;

(14) After the silica gel is removed from the ileum mold, and then trimmed to a certain extent, a bionic ileum silica gel model can be obtained that has the physiological structure of the ileum, intestinal wall folds and villi, and the villi can secrete intestinal juice.

Comparative Example 3: Preparation of bionic ileum (increased thickness of smeared silica gel)

(1) Prepare clay: knead the soft clay repeatedly to obtain soft clay with good ductility;

(2) Ileum mold pressing: Put the kneaded soft clay into the precise human ileum anatomical model of the medical gastroenterology department, squeeze it hard, remove the human ileum anatomical model, and obtain the soft clay ileum with the real internal physiological structure of the ileum Mold, the diameter of the mold is 2cm, and the length is 30cm;

(3) Production of hollow fluff: Take a number of needles with a diameter of 0.4mm, stick them on each imprint on the above mold, poke a small hole with a diameter of 0.6mm and a depth of 5mm, and the needles will continue to remain inside the mold

(4) Bake molding of the ileum mold: Put the ileum mold into an oven and bake at 130°C for 30 minutes to solidify the ileum mold and cool naturally to obtain a bionic ileum mold;

(8) Prepare silica gel: put transparent silica gel, silicone oil, and curing agent ethyl orthosilicate in a ratio of 100:2.5:1.5 in a beaker, stir well, and mix evenly;

(9) Put the uniformly mixed silica gel into a vacuum machine, under a negative pressure of 0.09MPa, vacuumize and debubble for 5 minutes, and obtain a bubble-free silica gel;

(10) Apply bubble-free silica gel evenly on the surface of the bionic ileum mold obtained above, with a thickness of about 6 mm;

(11) Leave the evenly smeared ileum mold for 2 hours to make it completely solidified and formed, then pull out the needle outside the mold to obtain a hollow ileum silica gel model with small intestinal villi;

(12) Cover the surface of the above-mentioned ileum mold with only the needle removed and the silica gel that has not fallen off with a piece of oily paper, and place a hollow cylinder with a diameter of 2 cm and a height of 4 cm on the outside, and fix it;

(13) Evenly apply bubble-free silica gel to the gap between the oily paper of the ileum mold and the cylinder, and let it stand for 2 hours until it is completely solidified and formed;

(14) Place the solidified silicone mold in water for 10 minutes, and after the water softens the oily paper, take out the oily paper from the hollow cylinder;

(15) After the silica gel is removed from the ileum mold, and then after a certain trimming process, a bionic ileum silica gel model with the physiological structure of the ileum, intestinal wall folds and villi, and the villi can secrete intestinal juice can be obtained.

Comparative Example 4: Preparation of bionic ileum (without adding silicone oil)

(1) Prepare clay: knead the soft clay repeatedly to obtain soft clay with good ductility;

(2) Ileum mold pressing: Put the kneaded soft clay into the precise human ileum anatomical model of the medical gastroenterology department, squeeze it hard, remove the human ileum anatomical model, and obtain the soft clay ileum with the real internal physiological structure of the ileum Mold, the diameter of the mold is 2cm, and the length is 30cm;

(3) Production of hollow fluff: Take a number of needles with a diameter of 0.4mm, stick them on each imprint on the above mold, poke a small hole with a diameter of 0.6mm and a depth of 5mm, and the needles will continue to remain inside the mold

(4) Bake molding of the ileum mold: Put the ileum mold into an oven and bake at 130°C for 30 minutes to solidify the ileum mold and cool naturally to obtain a bionic ileum mold;

(8) Prepare silica gel: put transparent silica gel and curing agent ethyl orthosilicate in a beaker at a ratio of 100:1, stir thoroughly, and mix evenly;

(9) Put the uniformly mixed silica gel into a vacuum machine, under a negative pressure of 0.09MPa, vacuumize and debubble for 5 minutes, and obtain a bubble-free silica gel;

(10) Apply bubble-free silica gel evenly on the surface of the bionic ileum mold obtained above, with a thickness of about 2mm;

(11) Leave the evenly smeared ileum mold for 2 hours to make it completely solidified and formed, then pull out the needle outside the mold to obtain a hollow ileum silica gel model with small intestinal villi;

(12) Cover the surface of the above-mentioned ileum mold with only the needle removed and the silica gel that has not fallen off with a piece of oily paper, and place a hollow cylinder with a diameter of 2 cm and a height of 4 cm on the outside, and fix it;

(13) Evenly apply bubble-free silica gel to the gap between the oily paper of the ileum mold and the cylinder, and let it stand for 2 hours until it is completely solidified and formed;

(14) Place the solidified silicone mold in water for 10 minutes, and after the water softens the oily paper, take out the oily paper from the hollow cylinder;

(15) After the silica gel is removed from the ileum mold, and then after a certain trimming process, a bionic ileum silica gel model with the physiological structure of the ileum, intestinal wall folds and villi, and the villi can secrete intestinal juice can be obtained.

Comparative Example 5: Preparation of bionic ileum (addition of glycerol)

(1) Prepare clay: knead the soft clay repeatedly to obtain soft clay with good ductility;

(2) Ileum mold pressing: Put the kneaded soft clay into the precise human ileum anatomical model of the medical gastroenterology department, squeeze it hard, remove the human ileum anatomical model, and obtain the soft clay ileum with the real internal physiological structure of the ileum Mold, the diameter of the mold is 2cm, and the length is 30cm;

(3) Production of hollow fluff: Take a number of needles with a diameter of 0.4mm, stick them on each imprint on the above mold, poke a small hole with a diameter of 0.6mm and a depth of 5mm, and the needles will continue to remain inside the mold

(4) Bake molding of the ileum mold: Put the ileum mold into an oven and bake at 130°C for 30 minutes to solidify the ileum mold and cool naturally to obtain a bionic ileum mold;

(8) Prepare silica gel: put transparent silica gel, glycerin and curing agent ethyl orthosilicate in a beaker at a ratio of 100:3:1, stir well, and mix well;

(9) Put the uniformly mixed silica gel into a vacuum machine, under a negative pressure of 0.09MPa, vacuumize and debubble for 5 minutes, and obtain a bubble-free silica gel;

(10) Apply bubble-free silica gel evenly on the surface of the bionic ileum mold obtained above, with a thickness of about 2 mm;

(11) Leave the evenly smeared ileum mold for 2 hours to make it completely solidified and formed, then pull out the needle outside the mold to obtain a hollow ileum silica gel model with small intestinal villi;

(12) Cover the surface of the above-mentioned ileum mold with only the needle removed and the silica gel that has not fallen off with a piece of oily paper, and place a hollow cylinder with a diameter of 2 cm and a height of 4 cm on the outside, and fix it;

(13) Evenly apply bubble-free silica gel to the gap between the oily paper of the ileum mold and the cylinder, and let it stand for 2 hours until it is completely solidified and formed;

(14) Place the solidified silicone mold in water for 10 minutes, and after the water softens the oily paper, take out the oily paper from the hollow cylinder;

(15) After the silica gel is removed from the ileum mold, and then after a certain trimming process, a bionic ileum silica gel model with the physiological structure of the ileum, intestinal wall folds and villi, and the villi can secrete intestinal juice can be obtained.

Example 4: Detection of bionic ileum

Take the human ileum anatomical model of the same length, the bionic ileum prepared in Example 1-3, the bionic ileum prepared in Comparative Example 1-5, and similar foreign products (purchased from the Fast 3 silicone bionic ileum of Dragon Skin Company in the United States) Intestinal area, transparency, hardness, swelling rate, elasticity, and villi function were tested. The test results are shown in Table 1.

It can be seen from Table 1 that the index comparison between the bionic ileum of the present invention and the real ileum is relatively close, and compared with similar foreign products, the index is better. Therefore, the bionic ileum of the present invention can replace the real ileum to predict in vivo tests, completely replace or partially replace In vivo experiments can achieve the purpose of reducing cost and time, improving repeatability and accuracy, and there is no theoretical limit.

Table 1 performance test results

Although the present invention has been disclosed above with preferred embodiments, it is not intended to limit the present invention. Any person familiar with this technology can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore The scope of protection of the present invention should be defined by the claims.

Claims (44)

1. A method for preparing a bionic ileum, characterized in that, the method is to put plastic materials into an accurate human ileum anatomical model in the Department of Gastroenterology of Medicine for modeling, take off the human ileum anatomical model, and place plastic materials in each of the plastic materials and Use a needle to poke a small hole in the depression corresponding to the villi of the small intestine on the anatomical model of the human ileum, keep the needle on the plastic material and solidify the plastic material to obtain an ileum mold with a real internal physiological structure of the ileum; According to a certain mass ratio, the base material and auxiliary materials for making the bionic ileum are mixed to obtain the raw material of the bionic ileum; according to a certain thickness, the raw material of the bionic ileum is applied to the side of the ileum mold that is in contact with the anatomical model of the human ileum, and it is left to stand so that the smear is on the The bionic ileum raw material on the surface of the ileum mold is solidified and formed, the needle is pulled out and the ileum mold is removed to obtain a hollow bionic ileum with small intestinal villi; Or the method is to put the plastic material into the accurate human ileum anatomical model of the medical department of gastroenterology for modeling, take off the human ileum anatomical model, and use the plastic material in each depression corresponding to the small intestinal villi on the human ileal anatomical model The needles poke out small holes, keep the needles on the plastic material and solidify the plastic material to obtain the ileum mold with the real internal physiological structure of the ileum; according to a certain mass ratio, the base material and Mix the auxiliary materials to obtain the bionic ileum raw material; apply the bionic ileum raw material on the side of the ileum mold that is in contact with the human ileum anatomical model according to a certain thickness, and let it stand to make the bionic ileum raw material coated on the surface of the ileum mold solidify and form, and only pull out A needle-shaped object to obtain a hollow bionic ileum with villi of the small intestine; a layer of spacer is covered on the side of the bionic ileum that is not in contact with the ileum mold, and the raw material of the bionic ileum is smeared on the side of the bionic ileum that is not in contact with the bionic ileum according to a certain thickness. On the side that is in contact, let it stand still to solidify the bionic ileum raw material applied on the surface of the spacer, remove the spacer and take off the ileum mold, and obtain a bionic ileum that has the villi of the ileum physiological structure and can secrete intestinal juice; The base material includes one or more of silica gel, latex or hydrogel; the auxiliary material includes silicone oil and/or curing agent. 2. The preparation method of a kind of bionic ileum as claimed in claim 1, is characterized in that, described plastic material comprises clay, paraffin, glass or steel. 3. A method for preparing a bionic ileum according to claim 1 or 2, characterized in that the diameter of the small hole is 0.2-1 mm. 4. The preparation method of a kind of bionic ileum as claimed in claim 1, is characterized in that, when described in each of the plastic material and the corresponding depression of small intestine villi on human body ileum anatomical model poked out the small hole, should make The needle penetrates the plastic material and makes one end of the needle protrude at least 2 mm from the side of the plastic material that is in contact with the anatomical model of the human ileum. 5. The preparation method of a kind of bionic ileum as claimed in claim 2, is characterized in that, when described in each of the plastic material and the corresponding depression of small intestine villi on the human ileum anatomical model poke out the small hole, should make The needle penetrates the plastic material and makes one end of the needle protrude at least 2 mm from the side of the plastic material that is in contact with the anatomical model of the human ileum. 6. The preparation method of a kind of bionic ileum as claimed in claim 3, is characterized in that, when described in each of the plastic material and the depression corresponding to the small intestine villi on the human ileum anatomical model poke out the small hole, should make The needle penetrates the plastic material and makes one end of the needle protrude at least 2 mm from the side of the plastic material that is in contact with the anatomical model of the human ileum. 7. The preparation method of a kind of bionic ileum as claimed in claim 1, is characterized in that, the mass ratio among described base material, silicone oil and curing agent is 100:(2.5～3.5):(0.5～1.5). 8 . The method for preparing a bionic ileum according to claim 2 , wherein the mass ratio between the base material, silicone oil and curing agent is 100:(2.5-3.5):(0.5-1.5). 9. A method for preparing a bionic ileum as claimed in claim 3, wherein the mass ratio between the base material, silicone oil and curing agent is 100:(2.5-3.5):(0.5-1.5). 10. A method for preparing a bionic ileum as claimed in claim 4, characterized in that the mass ratio between the base material, silicone oil and curing agent is 100:(2.5-3.5):(0.5-1.5). 11. The preparation method of a kind of bionic ileum as claimed in claim 1, is characterized in that, described bionic ileum raw material can be applied on the ileum mold only after vacuumizing and defoaming; the condition of described vacuumizing and defoaming is Vacuum machine negative pressure -0.1 ~ 0.09MPa, time 5 ~ 10min. 12. The preparation method of a kind of bionic ileum as claimed in claim 2, is characterized in that, described bionic ileum raw material can be applied on the ileum mold only after vacuumizing and defoaming; the condition of described vacuumizing and defoaming is Vacuum machine negative pressure -0.1 ~ 0.09MPa, time 5 ~ 10min. 13. The preparation method of a kind of bionic ileum as claimed in claim 3, is characterized in that, described bionic ileum raw material can be applied on the ileum mold only after vacuumizing and defoaming; the condition of described vacuumizing and defoaming is Vacuum machine negative pressure -0.1 ~ 0.09MPa, time 5 ~ 10min. 14. The preparation method of a kind of bionic ileum as claimed in claim 4, is characterized in that, described bionic ileum raw material can be applied on the ileum mold only after vacuumizing and defoaming; the condition of described vacuumizing and defoaming is Vacuum machine negative pressure -0.1 ~ 0.09MPa, time 5 ~ 10min. 15. The preparation method of a kind of bionic ileum as claimed in claim 5, is characterized in that, described bionic ileum raw material can be applied to the ileum mold after vacuumizing and defoaming; the condition of described vacuumizing and defoaming is Vacuum machine negative pressure -0.1 ~ 0.09MPa, time 5 ~ 10min. 16 . The method for preparing a bionic ileum according to claim 1 , wherein the thickness of the raw material of the bionic ileum applied on the surface of the ileum mold is 2-3 mm. 17 . The method for preparing a bionic ileum according to claim 2 , wherein the thickness of the raw material of the bionic ileum applied on the surface of the ileum mold is 2-3 mm. 18 . The method for preparing a bionic ileum according to claim 3 , wherein the thickness of the raw material of the bionic ileum applied on the surface of the ileum mold is 2-3 mm. 19 . The method for preparing a bionic ileum according to claim 4 , wherein the thickness of the raw material of the bionic ileum applied on the surface of the ileum mold is 2-3 mm. 20 . The method for preparing a bionic ileum according to claim 5 , wherein the thickness of the raw material of the bionic ileum applied on the surface of the ileum mold is 2-3 mm. 21 . 21. A method for preparing a bionic ileum according to claim 6, characterized in that the thickness of the bionic ileum raw material applied on the surface of the ileum mold is 2-3 mm. 22. The preparation method of a bionic ileum according to claim 1, characterized in that, the standing time is 2-4 hours. 23. The preparation method of a bionic ileum according to claim 2, characterized in that, the standing time is 2-4 hours. 24. The preparation method of a bionic ileum according to claim 3, characterized in that, the standing time is 2-4 hours. 25. The preparation method of a bionic ileum according to claim 4, characterized in that, the standing time is 2-4 hours. 26. The preparation method of a bionic ileum according to claim 5, characterized in that, the standing time is 2-4 hours. 27. The preparation method of a bionic ileum according to claim 6, characterized in that, the standing time is 2-4 hours. 28. The preparation method of a bionic ileum according to claim 7, characterized in that, the standing time is 2-4 hours. 29. The bionic ileum prepared by the method for preparing a bionic ileum according to claim 1. 30. The bionic ileum prepared by the method for preparing a bionic ileum according to claim 2. 31. The bionic ileum prepared by the method for preparing a bionic ileum according to claim 3. 32. The bionic ileum prepared by the method for preparing a bionic ileum according to claim 4. 33. The bionic ileum prepared by the method for preparing a bionic ileum according to claim 5. 34. The bionic ileum prepared by the method for preparing a bionic ileum according to claim 6. 35. The bionic ileum prepared by the method for preparing a bionic ileum according to claim 7. 36. The bionic ileum prepared by the method for preparing a bionic ileum according to claim 8. 37. The method for preparing a bionic ileum according to claim 1 or the application of the bionic ileum prepared according to any one of claims 29-36 in simulating the actual digestive system of a human body. 38. The method for preparing a bionic ileum according to claim 2 or the application of the prepared bionic ileum according to any one of claims 29-36 in simulating the actual digestive system of a human body. 39. The method for preparing a bionic ileum according to claim 3 or the application of the prepared bionic ileum according to any one of claims 29-36 in simulating the actual digestive system of a human body. 40. The method for preparing a bionic ileum according to claim 4 or the application of the prepared bionic ileum according to any one of claims 29-36 in simulating the actual digestive system of a human body. 41. The method for preparing a bionic ileum according to claim 5 or the application of the prepared bionic ileum according to any one of claims 29-36 in simulating the actual digestive system of a human body. 42. The method for preparing a bionic ileum according to claim 6 or the application of the prepared bionic ileum according to any one of claims 29-36 in simulating the actual digestive system of a human body. 43. The method for preparing a bionic ileum according to claim 7 or the application of the bionic ileum prepared according to any one of claims 29-36 in simulating the actual digestive system of a human body. 44. The method for preparing a bionic ileum according to claim 8 or the application of the prepared bionic ileum according to any one of claims 29-36 in simulating the actual digestive system of a human body.