Bionic Digestive Tract as well as Preparation Method and Application Thereof
20230306875 · 2023-09-28
Inventors
- Minjie Gao (Wuxi, CN)
- Zhitao Li (Wuxi, CN)
- Xiaobei Zhan (Wuxi, CN)
- Li Zhu (Wuxi, CN)
- Wenlong Zhang (Wuxi, CN)
- Jingjing Xu (Wuxi, CN)
- Yun Jiang (Wuxi, CN)
Cpc classification
B29C41/02
PERFORMING OPERATIONS; TRANSPORTING
B29K2083/005
PERFORMING OPERATIONS; TRANSPORTING
B29B13/00
PERFORMING OPERATIONS; TRANSPORTING
B29L2031/7532
PERFORMING OPERATIONS; TRANSPORTING
B29B2013/005
PERFORMING OPERATIONS; TRANSPORTING
International classification
B29B13/00
PERFORMING OPERATIONS; TRANSPORTING
Abstract
The disclosure discloses a bionic digestive tract as well as a preparation method and application thereof, belonging to the field of bionic technologies and the field of biological technologies. The bionic digestive tract of the disclosure is prepared by mixing a base material (one or more of silica gel, latex and hydrogel) and auxiliary materials (silicone oil and a curing agent) in a certain mass ratio (the mass ratio of the base material to the silicone oil to the curing agent is 100:(0.5 to 10):(0.5 to 3.5)). The simulation performance of the bionic digestive tract is excellent, has strong consistency with a true human digestive tract in terms of performance, structure and function, can simulate the true states of food, drugs and microorganisms in a digestive system, and has great application prospects in the research process of food and drugs.
Claims
1. A preparation method of a bionic large intestine, comprising steps of: firstly preparing a large intestine mould having an interior physiological structure of a true large intestine, then smearing a bionic large intestine raw material on a surface of the large intestine mould according to a certain thickness, standing so as to solidify and mold the bionic large intestine raw material, and removing the mould so as to obtain the bionic large intestine, wherein the preparing the large intestine mould having the interior physiological structure of the true large intestine comprises steps of: filling a large intestine of a precise human large intestinal tract anatomical model of a medicine gastroenterology department with a plastic material, then taking out the large intestine of the precise large intestinal tract anatomical model of the medicine gastroenterology department, and solidifying and molding the plastic material to obtain the large intestine mould having the interior physiological structure of the true large intestine; the bionic large intestine raw material is obtained by mixing a base material and auxiliary materials that are used for preparing the bionic large intestine in a certain mass ratio and then putting the mixture into a vacuum machine for vacuumizing and removing bubbles; the base material comprises of silica gel, latex and hydrogel; and the auxiliary materials comprise silicone oil and a curing agent.
Description
BRIEF DESCRIPTION OF FIGURES
[0148]
[0149]
[0150]
[0151]
[0152]
[0153]
[0154]
DETAILED DESCRIPTION
[0155] Detection methods involved in the following examples are as follows:
[0156] A detection method of an area in stomach is as follows:
S=2π(r.sub.1h.sub.1+r.sub.2h.sub.2+r.sub.3h.sub.3)+n.sub.1(π−1)r.sub.1h.sub.1+n.sub.2(π−1)r.sub.2h.sub.2+n.sub.3(π−1)r.sub.3h.sub.3,
[0157] wherein S is the area in a stomach, r.sub.1 is the radius of a stomach fundus, h.sub.1 is the height of the stomach fundus, n.sub.1 is the quantity of stomach fundus walls, r.sub.2 is the radius of a stomach body, h.sub.2 is the height of the stomach body, n.sub.2 is the quantity of stomach body walls, r.sub.3 is the radius of a stomach antrum, h.sub.3 is the height of the stomach antrum, and n.sub.3 is the quantity of the stomach antrum.
[0158] A detection method of an intestinal area is as follows:
S=2πr.sub.1h.sub.1+n(n−1)r.sub.2h.sub.2,
[0159] wherein S is the intestinal area, r.sub.1 is the radius of an intestine, h.sub.1 is the height of intestine, n is the quantity of intestine walls, r.sub.2 is the radius of the intestine wall, and h.sub.2 is the height of the intestine wall.
[0160] A Detection Method of a Food Grinding Function is as Follows:
[0161] The obtained bionic stomach fundus, bionic stomach body and bionic antrum/bionic stomach are wholly fixed in a stomach body visualization bionic reactor (the stomach body visualization bionic reactor is seen in the invention patent No. CN108088966A) through a flange interface of a pipeline. 100 g of raw rice, with the particle size of about 1 mm, is taken and added into the bionic stomach, the reactor runs for 10 min, and the rice is taken out to observe whether the particle size is smaller.
[0162] A Detection Method of a Back Flow Function is as Follows:
[0163] The bionic stomach is fixed in a stomach body visualization bionic reactor (the stomach body visualization bionic reactor is seen in the invention patent No.: CN108088966A), 100 ml of milk is added, the flow solenoid valve of the reactor is opened by running the reactor to give pressure to the bionic gastric antrum to see whether the “back flow function” of milk in the gastric antrum flowing back to the stomach body can be realized.
[0164] A Transparency Detection Method is as Follows:
[0165] Whether the silica gel is transparent and has bubbles is observed by visual inspection. The silica gel is stretched to see whether it is white. The white one is opaque. Rice, corn and other foods are put into the inside of the silica gel to see whether the appearance of the food can be clearly seen.
[0166] If the surface of food can be clearly seen, the transparency is good; if the outline of food can be seen, the transparency is moderate; if the image of food cannot be seen, the transparency is poor.
[0167] A hardness (Shore hardness) detection method is as follows:
[0168] The hardness is measured using a Shore hardmeter. The needle of the hardmeter is pressed on the surface of the stomach to measure the depth of the needle pressed into the surface of the stomach.
[0169] An expansion rate test method is as follows:
Pe=(W*m/A)×100%,
[0170] wherein Pe is the expansion rate, W is the total balance load, A is the area of silica gel, and m is the lever ratio of the pressurized equipment.
[0171] An elasticity detection method is as follows:
[0172] The tensile test of silica gel is carried out on a tensile testing machine to measure the axial elongation and transverse elongation of silica gel until the silica gel is broken.
C=(D−d)×100%/d,
[0173] wherein C is the elastic rate, D is the elongation, and d is the initial length of silica gel.
[0174] Detection of intestinal juice secretion function of villi:
[0175] The obtained bionic duodenum is fixed in an intestinal visualized bionic reactor through the flange interface of the pipe (the intestinal visualized bionic reactor is seen in the invention patent NO.: CN108318625A), 100 ml of pancreatic juice is added into the bionic silica gel duodenum, the reactor is operated for 10 min, and the volume of pancreatic juice is observed.
Example 1.1: Preparation of Bionic Stomach
[0176] (1) preparation of the clay: soft clay was kneaded repeatedly to obtain soft clay having good malleability; [0177] (2) pressing of a stomach fundus mould: the kneaded soft clay was put into a stomach fundus of a precise human stomach anatomical model of a medicine gastroenterology department and strongly squeezed, and the human stomach anatomical model was taken out to obtain a soft clay stomach fundus mould having the interior physiological structure of a true stomach fundus; [0178] (3) baking and molding of the stomach fundus mould: the stomach fundus mould was put into an oven and baked for 15 minutes so that the stomach fundus mould was solidified and molded and then naturally cooled, so as to obtain a bionic stomach fundus mould; [0179] (4) pressing of a stomach body mould: the kneaded soft clay was put into a stomach body of the precise human stomach anatomical model of the medicine gastroenterology department and strongly squeezed, and the human stomach anatomical model was taken out to obtain a soft clay stomach body mould having the interior physiological structure of the true stomach body; [0180] (5) baking and molding of the stomach body mould: the stomach body mould was put into the oven and baked for 15 minutes so that the stomach body mould was solidified and molded and then naturally cooled, so as to obtain the bionic stomach body mould; [0181] (6) pressing of a stomach antrum mould: the kneaded soft clay was put into a stomach antrum of the precise human stomach anatomical model of the medicine gastroenterology department and strongly squeezed, and the human stomach anatomical model was taken out to obtain the soft clay stomach antrum mould having the interior physiological structure of the true stomach antrum; [0182] (7) baking and molding of the stomach antrum mould: the stomach antrum mould was put into the oven and baked for 15 minutes so that the stomach antrum mould was solidified and molded and then naturally cooled, so as to obtain the bionic stomach antrum mould; [0183] (8) preparation of silica gel: transparent silica gel, silicone oil and a curing agent tetrathoxysilane were placed in a beaker in a ratio of 100:8:2, sufficiently mixed and uniformly mixed; [0184] (9) the uniformly mixed silica gel was put into a vacuum machine, vacuumized at a negative pressure of 0.09 MPa to remove the bubbles for 5 minutes to obtain a bubble-free silica gel; [0185] (10) the bubble-free silica gel was uniformly smeared on the surface of the bionic stomach fundus, stomach body and stomach antrum moulds, with a thickness of about 1 mm; [0186] (11) the three uniformly smeared moulds stood for 2 hours so that the moulds could be completely solidified and molded. After the moulds were removed, and after certain pruning, a bionic silica gel stomach fundus, a bionic silica gel stomach body and a bionic silica gel stomach antrum were obtained.
Example 1.2: Preparation of Bionic Stomach
[0187] On the basis of example 1.1, the mould baking time in steps (3), (5) and (7) was changed to 20 min, the curing agent in step (8) was changed to diaminodiphenyl-methane (DDM), and meanwhile the mass ratio of transparent silica gel to silicone oil to the curing agent was 100:7:1.5; the bubble removing time in step (9) was changed to 10 min; the smearing thickness in step (10) was changed to 2 mm; and the standing time in step (11) was changed to 4 h.
Example 1.3: Preparation of Bionic Stomach
[0188] On the basis of example 1.1, the mould baking time in steps (3), (5) and (7) was changed to 30 min, the curing agent in step (8) was changed to vinyl triamine, and meanwhile the mass ratio of transparent silica gel to silicone oil to the curing agent was changed to 100:9:3; the smearing thickness in step (10) was changed to 3 mm; and the standing time in step (11) was changed to 1 h.
Comparative Example 1.1: Preparation of Bionic Stomach (without Interior Biological Structure of Stomach)
[0189] On the basis of example 1.1, step (2) is changed to: the kneaded soft clay was made into the shape of a stomach fundus having a smooth surface to obtain the stomach fundus mould; step (4) is changed to: the kneaded soft clay was made into the shape of a stomach body having a smooth surface to obtain the stomach body mould; step (6) is changed to: the kneaded soft clay was made into the shape of a stomach antrum having a smooth surface to obtain the stomach antrum mould; the mould baking time in steps (3), (5) and (7) was changed to 30 min; the mass ratio of transparent silica gel to silicone oil to the curing agent in step (8) was changed to 100:5:2; and the smearing thickness in step (10) was changed to 2 mm.
Comparative Example 1.2: Preparation of Bionic Stomach (Whole Stomach Model)
[0190] On the basis of example 1.1, steps (2) to (7) were changed to: the kneaded soft clay was made into the shape of a stomach having a smooth surface to obtain a stomach fundus mould, the stomach mould was put into the oven to be baked for 30 min so that the stomach mould was solidified and molded and then naturally cooled to obtain a stomach mould; the mass ratio of transparent silica gel to silicone oil to the curing agent in step (8) was changed to 100:6:1; and the smearing thickness in step (10) was 2 mm.
Comparative Example 1.3: Preparation of Bionic Stomach (after Mixing, the Silica Gel is not Vacuumized)
[0191] On the basis of example 1.1, the mould baking time in steps (3), (5) and (7) was changed to 30 min; the mass ratio of transparent silica gel to silicone oil to the curing agent in step (8) was changed to 100:10:3; step (9) was omitted; the smearing thickness in step (10) was changed to 3 mm; and the standing time in step (11) was changed to 1 h.
Comparative Example 1.4: Preparation of Bionic Stomach (the Thickness of Smeared Silica Gel is Increased)
[0192] On the basis of example 1.1, the mould baking time in steps (3), (5) and (7) was changed to 30 min; the mass ratio of transparent silica gel to silicone oil to the curing agent in step (8) was changed to 100:8:2; step (9) was omitted; the smearing thickness in step (10) was changed to 6 mm; the standing time in step (11) was changed to 1 h.
Comparative Example 1.5: Preparation of Bionic Stomach (without Addition of Silicone Oil)
[0193] On the basis of example 1.1, the mould baking time in steps (3), (5) and (7) was changed to 30 min; the silicone oil in step (8) was omitted, meanwhile, the mass ratio of transparent silica gel to the curing agent was changed to 100:3; the smearing thickness in step (10) was changed to 2 mm; and the standing time in step (11) was changed to 1 h.
Comparative Example 1.6: Preparation of Bionic Stomach (with Addition of Glycerinum)
[0194] On the basis of example 1.1, the mould baking time in steps (3), (5) and (7) was changed to 30 min; the silicone oil in step (8) was replaced with glycerinum; the smearing thickness in step (10) was changed to 2 mm; and the standing time in step (11) was 1 h.
Example 1.4: Detection of Bionic Stomach
[0195] The anatomical model of a human stomach, the bionic stomachs prepared in examples 1.1 to 1.3, the bionic stomachs prepared in comparative examples 1.1 to 1.6 and the similar foreign products (Fast 10 model of bionic silica gel stomachs purchased from American Dragon Skin company) were subjected to detection of intragastric area, food grinding function, back flow function, transparency, hardness, expansion rate and elasticity. The detection results are shown in Table 1.
[0196] It can be seen from Table 1 that the indexes of the bionic stomachs and the true stomach of the disclosure are relatively close by comparison, and compared with the similar foreign products, the indexes are better. Therefore, the bionic stomachs of the disclosure can replace the true stomach to predict the live test, and can completely or partially replace the live test, so as to reduce the cost and time and improve the repeatability and accuracy, and there is no theoretical limitation.
TABLE-US-00001 TABLE 1 Performance Test Result Whether a Human Whether “back flow” stomach Intragastric food is function is Transparent Expansion anatomical area grinded present effect Hardness rate Elasticity model 800 cm.sup.2 Yes Yes Opaque 69 35% 570% Example 790 cm.sup.2 Yes Yes Good 68 36% 550% 1.1 Example 800 cm.sup.2 Yes Yes Good 65 37% 560% 1.2 Example 790 cm.sup.2 Yes Yes Moderate 71 36% 540% 1.3 Comparative 400 cm.sup.2 No Yes Good 63 32% 520% example 1.1 Comparative 780 cm.sup.2 No No Good 62 33% 540% example 1.2 Comparative 780 cm.sup.2 Yes Yes Poor, and 72 38% 580% example bubbles 1.3 exist Comparative 790 cm.sup.2 Yes Yes Poor 70 35% 560% example 1.4 Comparative 800 cm.sup.2 Yes Yes Good 73 10% 530% example 1.5 Comparative 780 cm.sup.2 Yes Yes Good 59 25% 550% example 1.6 Similar 400 cm.sup.2 No No Good 30 10% 1000% foreign products
Example 2.1: Preparation of Bionic Large Intestine
[0197] (1) Preparation of clay: the soft clay was repeatedly kneaded to obtain soft clay having good malleability; [0198] (2) pressing of a large intestine mould: the kneaded soft clay was put into a precise human large intestine anatomical model of a medicine gastroenterology department and strongly squeezed, the human large intestine anatomical model was taken out to obtain a soft clay large intestine mould having the interior physiological structure of a true large intestine, and the mould is 4 cm in diameter and 25 cm in length; [0199] (3) baking and molding of the large intestine mould: the large intestine mould was put into an oven and baked for 15 minutes at 140° C. so that the large intestine mould was solidified and molded and then naturally cooled, so as to obtain the bionic large intestine mould; [0200] (4) preparation of silica gel: transparent silica gel, silicone oil and a curing agent were placed in a beaker in a ratio of 100:5:2, sufficiently stirred and uniformly mixed; [0201] (5) the uniformly mixed silica gel was put into a vacuum machine, and vacuumized at a negative pressure of 0.09 MPa to remove the bubbles for 5 minutes to obtain bubble-free silica gel; [0202] (6) the bubble-free silica gel was uniformly smeared on the surface of the above bionic large intestine mould, with a thickness of about 1 mm; [0203] (7) the uniformly smeared large intestine mould stood for 2 hours so that the mould was completely solidified and molded; and [0204] (8) after the silica gel was removed from the large intestine mould, and after certain pruning, the bionic large intestine silica gel mould having intestine wall corrugations of the large intestine physiological structure was obtained.
Example 2.2: Preparation of Bionic Large Intestine
[0205] On the basis of example 2.1, the diameter of the mould in step (2) was changed to 4.5 cm; the curing agent in step (4) was replaced with vinyl triamine, and meanwhile the mass ratio of transparent silica gel to silicone oil to the curing agent was changed to 100:4:1; the smearing thickness in step (6) was changed to 2 mm; and the standing time in step (7) was changed to 4 h.
Example 2.3: Preparation of Bionic Large Intestine
[0206] On the basis of example 2.1, the diameter of the mould in step (2) was changed to 5 cm; the curing agent in step (4) was replaced with diaminodiphenyl-methane (DDM), and meanwhile the mass ratio of transparent silica gel to silicone oil to the curing agent was changed to 100:6:3; and the smearing thickness in step (6) was changed to 3 mm.
Comparative Example 2.1: Preparation of Bionic Large Intestine (without Corrugations)
[0207] On the basis of example 2.1, step (2) is changed to: the kneaded soft clay was made into a long cylinder having a smooth surface, and the mould was 4 cm in diameter and 30 cm in length; the baking conditions in step (3) were changed to: baking was conducted for 30 min at 130°; the mass ratio of transparent silica gel to silicone oil to the curing agent in step (4) was changed to 100:5:3; the smearing thickness in step (6) was changed to 2 mm; and the standing time in step (7) was changed to 1 h.
Comparative Example 2.2: Preparation of Bionic Large Intestine (Silica Gel is not Vacuumized after Mixing)
[0208] On the basis of example 2.1, the diameter of the mould in step (2) was changed to 4.5 cm; the baking conditions in step (3) were changed to: baking was conducted for 30 min at 130° i; the mass ratio of transparent silica gel to silicone oil to the curing agent in step (4) was changed to 100:6:2; step (5) was omitted; and the smearing thickness in step (6) was changed to 2 mm.
Comparative Example 2.3: Preparation of Bionic Large Intestine (the Thickness of the Smeared Silica Gel is Increased)
[0209] On the basis of example 2.1, the diameter of the mould in step (2) was changed to 5 cm; the baking conditions in step (3) were changed to: baking was conducted for 30 min at 130° i; the curing agent in step (4) was replaced with vinyl triamine, and meanwhile the mass ratio of transparent silica gel to silicone oil to the curing agent was changed to 100:3:3; and the smearing thickness in step (6) was changed to 8 mm.
Comparative Example 2.4: Preparation of Bionic Large Intestine (without Addition of Silicone Oil)
[0210] On the basis of example 2.1, the diameter of the mould in step (2) was changed to 5 cm; the baking conditions in step (3) were changed to: baking was conducted for 15 min at 150° i; the silicone oil in step (4) was omitted, and meanwhile the mass ratio of transparent silica gel to the curing agent was changed to 100:3; and the smearing thickness in step (6) was changed to 2 mm.
Comparative Example 2.5: Preparation of Bionic Large Intestine (with Addition of Glycerinum)
[0211] On the basis of example 2.1, the diameter of the mould in step (2) was changed to 5 cm; the baking conditions in step (3) were changed to: baking was conducted for 15 min at 150° i; the silicone oil in step (4) was replaced with glycerinum; and the smearing thickness in step (6) was changed to 2 mm.
Example 2.4: Detection of Bionic Large Intestine
[0212] The human large intestine anatomical model, the bionic large intestines prepared in examples 2.1 to 2.3, the bionic large intestines prepared in comparative examples 2.1 to 2.5 and the similar foreign products (Fast 6 model of bionic silica gel large intestines purchased from American Dragon Skin company), which are the same in length, were taken and subjected to detection of intestine area, transparency, hardness, expansion rate and elasticity. The detection results are shown in Table 2.
[0213] It can be seen from Table 2 that the indexes of the bionic large intestines of the disclosure and the true large intestine are relatively close by comparison, and compared with the similar foreign products, the indexes are better. Therefore, the bionic large intestines of the disclosure can replace the true large intestine to predict the live test, completely or partially replace the live test, so as to reduce the cost and time, improve the repeatability and accuracy, and there is no theoretical limitation.
TABLE-US-00002 TABLE 2 Performance Detection Results Intestinal Transparent Expansion Elas- area effect Hardness rate ticity Human large >600 cm.sup.2 Opaque 61 30% 420% intestine anatomical model Example 1 >600 cm.sup.2 Good 60 31% 460% Example 2 >600 cm.sup.2 Good 58 29% 430% Example 3 >600 cm.sup.2 Good 63 31% 470% Comparative <200 cm.sup.2 Good 64 30% 490% example 1 Comparative >600 cm.sup.2 Poor, and 59 33% 430% example 2 bubbles exist Comparative >600 cm.sup.2 Poor 63 28% 420% example 3 Comparative >600 cm.sup.2 Good 71 10% 520% example 4 Comparative >600 cm.sup.2 Good 58 20% 550% example 5 Similar <200 cm.sup.2 Good 30 10% 1000% foreign products
Example 3.1: Preparation of Bionic Ileum
[0214] (1) Preparation of the clay: soft clay was repeatedly kneaded to obtain soft clay having good malleability; [0215] (2) pressing of an ileum mould: the kneaded soft clay was put into a precise human ileum anatomical model of a medicine gastroenterology department and strongly squeezed, the human ileum anatomical model was taken out to obtain the soft clay ileum mould having the interior physiological structure of a true ileum, and the mould is 1.5 cm in diameter and 25 cm in length; [0216] (3) manufacturing of hollow villi: a plurality of needles having a diameter of 0.5 mm were taken and pricked on each imprint of the above mould to poke small holes having a diameter of 1 mm and a depth of 5 mm, and the needles continued to be kept inside the mould; [0217] (4) baking and molding of the ileum mould: the ileum mould was put into an oven and baked for 15 minutes at 140° w so that the ileum mould was solidified and molded and then naturally cooled, so as to obtain the bionic ileum mould; [0218] (5) preparation of silica gel: transparent silica gel, silicone oil and a curing agent were placed in a beaker in a ratio of 100:3:1, sufficiently stirred and uniformly mixed; [0219] (6) the uniformly mixed silica gel was put into a vacuum machine, vacuumized at a negative pressure of 0.09 MPa to remove the bubbles for 5 minutes to obtain bubble-free silica gel; [0220] (7) the bubble-free silica gel was uniformly smeared on the surface of the above bionic ileum mould, with a thickness of about 2 mm; [0221] (8) the uniformly smeared ileum mould stood for 2 hours so that the mould could be completely solidified and molded, and the needles outside the mould were pulled out to obtain an ileum silica gel model having intestinal villi and being hollow; [0222] (9) the surface of the ileum mould in which needles were only pulled out and silica gel does not fall off is covered with oily paper, a hollow cylinder having a diameter of 2 cm and height of 4 cm was placed outside the mould and well adhered and fixed; [0223] (10) bubble-free silica gel was uniformly smeared in a gap between the oily paper of the ileum mould and the cylinder, and standing was carried out for 2 h until the silica gel was completely solidified and molded; [0224] (11) the solidified silica gel mould was placed in water for 10 min, and the oily paper was taken out from the hollow cylinder after water softened the oily paper; and [0225] (12) after the silica gel was removed from the ileum mould, and after certain pruning, the bionic ileum silica gel model having intestine wall corrugations of the ileum physiological structure and villi capable of secreting intestinal juice was obtained.
Example 3.2: Preparation of Bionic Ileum
[0226] On the basis of example 3.1, the diameter of the mould in step (2) was changed to 2 cm; the diameter of the needle in step (3) was changed to 0.3 mm, and the diameter of the small hole was changed to 0.5 mm; the baking conditions in step (4) were changed to: baking was carried out for 20 min at 150° C.; the curing agent in step (5) was vinyl triamine, and meanwhile the mass ratio of transparent silica gel to silicone oil to the curing agent was changed to 100:3:1.5; the smearing thickness in step (7) was changed to 2.5 mm; the standing time in step (8) was changed to 4 h; the standing time in step (10) was changed to 1 h.
Example 3.3: Preparation of Bionic Ileum
[0227] On the basis of example 3.1, the diameter of the mould in step (2) was changed to 2.5 cm, and the length was changed to 30 cm; the diameter of the needle in step (3) was changed to 0.1 mm, and the diameter of the small hole was changed to 0.2 mm; the baking conditions in step (4) were changed to: baking was carried out for 30 min at 130° C.; the curing agent in step (5) was changed to diaminodiphenyl-methane (DDM), and meanwhile the mass ratio of transparent silica gel to silicone oil to the curing agent was 100:2.5:1; the smearing thickness in step (7) was changed to 3 mm; the standing time in step (8) was changed to 1 h; and the standing time in step (10) was changed to 1 h.
Comparative Example 3.1: Preparation of Bionic Ileum (without Villi)
[0228] On the basis of example 3.1, the diameter of the mould in step (2) was changed to 2.5 cm, and the length was changed to 30 cm; step (3) was omitted; the baking conditions in step (4) were changed to: baking was conducted for 30 min at 130° C.; the mass ratio of transparent silica gel to silicone oil to the curing agent in step (5) was changed to 100:3.5:0.5; the smearing thickness in step (7) was changed to 2.5 mm; step (8) was changed to: the uniformly smeared ileum mould stood for 1 h so as to be completely solidified and molded; and steps (9) to (11) were omitted.
Comparative Example 3.2: Preparation of Bionic Ileum (Silica Gel is not Vacuumized after Mixing)
[0229] On the basis of example 3.1, the diameter of the mould in step (2) was changed to 2 cm, and the length was changed to 30 cm; the diameter of the needle in step (3) was changed to 0.2 mm, and the diameter of the small hole was changed to 0.5 mm; the baking conditions in step (4) were changed to: baking was conducted for 20 min at 140° C.; the mass ratio of transparent silica gel to silicone oil to the curing agent in step (5) was changed to 100:3:0.5; step (6) was omitted; and the smearing thickness in step (7) was changed to 2.5 mm.
Comparative Example 3.3: Preparation of Bionic Ileum (the Thickness of the Smeared Silica Gel is Increased)
[0230] On the basis of example 3.1, the diameter of the mould in step (2) was changed to 2 cm, and the length was changed to 30 cm; the diameter of the needle in step (3) was changed to 0.4 mm, and the diameter of the small hole was changed to 0.6 mm; the baking conditions in step (4) were changed to: baking was conducted for 30 min at 130° C.; the mass ratio of transparent silica gel to silicone oil to the curing agent in step (5) was changed to 100:2.5:1.5; and the smearing thickness in step (7) was changed to 6 mm.
Comparative Example 3.4: Preparation of Bionic Ileum (without Addition of Silicone Oil)
[0231] On the basis of example 3.1, the diameter of the mould in step (2) was changed to 2 cm, and the length was changed to 30 cm; the diameter of the needle in step (3) was changed to 0.4 mm, and the diameter of the small hole was changed to 0.6 mm; the baking conditions in step (4) were changed to: baking was conducted for 30 min at 130° C.; and silicone oil in step (5) was omitted.
Comparative Example 3.5: Preparation of Bionic Ileum (with Addition of Glycerinum)
[0232] On the basis of example 3.1, the diameter of the mould in step (2) was changed to 2 cm, and the length was changed to 30 cm; the diameter of the needle in step (3) was changed to 0.4 mm, and the diameter of the small hole was changed to 0.6 mm; the baking conditions in step (4) were changed to: baking was conducted for 30 min at 130° C.; and silicone oil in step (5) was replaced with glycerinum.
Example 3.4: Detection of Bionic Ileum
[0233] The human ileum anatomical model, the bionic ilea prepared in examples 3.1 to 3.3, the bionic ilea prepared in comparative examples 3.1 to 3.5 and the similar foreign products (Fast 3 model of bionic silica gel ilea purchased from American Dragon Skin company), which are the same in length, were taken and subjected to detection of intestine area, transparency, hardness, expansion rate and elasticity. The detection results are shown in Table 3.
[0234] It can be seen from Table 3 that the indexes of the bionic ilea of the disclosure and the true ileum are relatively close by comparison, and compared with the similar foreign products, the indexes are better. Therefore, the bionic ilea of the disclosure can replace the true ileum to predict the live test, and can completely or partially replace the live test, so as to reduce the cost and time and improve the repeatability and accuracy, and there is no theoretical limitation.
TABLE-US-00003 TABLE 3 Performance Detection Results Whether villi have a function of Intestinal Transparent Expansion secreting area effect Hardness rate Elasticity intestinal juice Human ileum >3500 cm.sup.2 Opaque 32 28% 220% Yes anatomical model Example 1 >3500 cm.sup.2 Good 32 29% 240% Yes Example 2 >3500 cm.sup.2 Good 33 28% 220% Yes Example 3 >3500 cm.sup.2 Good 32 27% 210% Yes Comparative 300 cm.sup.2 Good 30 29% 230% No example 1 Comparative >3500 cm.sup.2 Poor, and 31 28% 220% Yes example 2 bubbles exist Comparative >3500 cm.sup.2 Poor 35 27% 210% Yes example 3 Comparative >3500 cm.sup.2 Good 56 12% 550% Yes example 4 Comparative >3500 cm.sup.2 Good 51 18% 500% Yes example 5 Similar foreign 300 cm.sup.2 Good 30 10% 1000% No products
Example 4.1: Preparation of Bionic Duodenum
[0235] (1) Preparation of clay: soft clay was repeatedly kneaded to obtain soft clay having good malleability; [0236] (2) pressing of a duodenum mould: the kneaded soft clay was put into a precise human duodenum anatomical model of a medicine gastroenterology department and strongly squeezed, the human duodenum anatomical model was taken out to obtain the soft clay duodenum mould having the interior physiological structure of a true duodenum, and the mould is 3 cm in diameter and 25 cm in length; [0237] (3) manufacturing of hollow villi: a plurality of needles having a diameter of 0.5 mm were taken and pricked each imprint of the above mould to poke so as to form small holes having a diameter of 1 mm and a depth of 5 mm, and the needles continued to be kept inside the mould; [0238] (4) baking and molding of the duodenum mould: the duodenum mould was put into an oven and baked for 15 minutes at 140° C. so that the duodenum mould was solidified and molded and then naturally cooled, so as to obtain the bionic duodenum mould; [0239] (5) preparation of silica gel: transparent silica gel, silicone oil and a curing agent tetraethoxysilane were placed in a beaker in a ratio of 100:1:3, sufficiently stirred and uniformly mixed; [0240] (6) the uniformly mixed silica gel was put into a vacuum machine, and vacuumized at a negative pressure of 0.09 MPa to remove the bubbles for 5 minutes to obtain bubble-free silica gel; [0241] (7) the bubble-free silica gel was uniformly smeared on the surface of the above bionic duodenum mould, with a thickness of about 1 mm; [0242] (8) the uniformly smeared duodenum mould stood for 2 hours so that the mould could be completely solidified and molded, and the needles outside the mould were pulled out to obtain a duodenum silica gel model having intestinal villi and being hollow; [0243] (9) the surface of the ileum mould in which needles were only pulled out and silica gel did not fall off is covered with oily paper, and a hollow cylinder having a diameter of 2 cm and height of 4 cm was placed outside the mould and well adhered and fixed; [0244] (10) bubble-free silica gel was uniformly smeared in a gap between the oily paper of the duodenum mould and the cylinder, and standing was carried out for 2 h until the silica gel was completely solidified and molded; [0245] (11) the solidified silica gel mould was placed in water for 10 min, and the oily paper was taken out from the hollow cylinder after water softened the oily paper; and [0246] (12) after the silica gel was removed from the duodenum mould, and after certain pruning, the bionic duodenum silica gel model having intestine wall corrugations of the duodenum physiological structure and villi capable of secreting intestinal juice was obtained.
Example 4.2: Preparation of Bionic Duodenum
[0247] On the basis of example 4.1, the diameter of the mould in step (2) was changed to 3.5 cm; the diameter of the needle in step (3) was changed to 0.3 mm, and the diameter of the small hole was changed to 0.5 mm; the baking conditions in step (4) were changed to: baking was carried out for 20 min at 150° C.; the curing agent in step (5) was changed to vinyl triamine, and meanwhile the mass ratio of transparent silica gel to silicone oil to the curing agent was changed to 100:1.5:3; the smearing thickness in step (7) was changed to 1.5 mm; the standing time in step (8) was changed to 4 h; and the standing time in step (10) was changed to 1 h.
Example 4.3: Preparation of Bionic Duodenum
[0248] On the basis of example 4.1, the diameter of the mould in step (2) was changed to 4 cm, and the length was changed to 30 cm; the diameter of the needle in step (3) was changed to 0.1 mm, and the diameter of the small hole was changed to 0.2 mm; the baking conditions in step (4) were changed to: baking was carried out for 30 min at 130° C.; the curing agent in step (5) was changed to diaminodiphenyl-methane (DDM), and meanwhile the mass ratio of transparent silica gel to silicone oil to the curing agent was changed to 100:1:2.5; the smearing thickness in step (7) was changed to 2 mm; the standing time in step (8) was changed to 1 h; and the standing time in step (10) was changed to 1 h.
Comparative Example 4.1: Preparation of Bionic Duodenum (without Villi)
[0249] On the basis of example 4.1, the length of the mould in step (2) was changed to 30 cm; step (3) was omitted; the baking conditions in step (4) were changed to: baking was conducted for 30 min at 130° C.; the mass ratio of transparent silica gel to silicone oil to the curing agent in step (5) was changed to 100:1:3; the smearing thickness in step (7) was changed to 1.5 mm; step (8) was changed to: the uniformly smeared duodenum mould stood for 1 h so that it was completely solidified and molded; and steps (9) to (11) were omitted.
Comparative Example 4.2: Preparation of Bionic Duodenum (Silica Gel is not Vacuumized after Mixing)
[0250] On the basis of example 4.1, the diameter of the mould in step (2) was changed to 3.5 cm, and length was changed to 30 cm; the diameter of the needle in step (3) was changed to 0.2 mm, and the diameter of the small hole was changed to 0.5 mm; the baking conditions in step (4) were changed to: baking was conducted for 20 min at 140° C.; the mass ratio of transparent silica gel to silicone oil to the curing agent in step (5) was changed to 100:0.5:2.5; step (6) was omitted; and the smearing thickness in step (7) was changed to 1.5 mm.
Comparative Example 4.3: Preparation of Bionic Duodenum (the Thickness of the Smeared Silica Gel is Increased)
[0251] On the basis of example 4.1, the diameter of the mould in step (2) was changed to 4 cm, and the length was changed to 30 cm; the diameter of the needle in step (3) was changed to 0.4 mm, and the diameter of the small hole was changed to 0.6 mm; the baking conditions in step (4) were changed to: baking was conducted for 30 min at 130° C.; the mass ratio of transparent silica gel to silicone oil to the curing agent in step (5) was changed to 100:1.5:3.5; and the smearing thickness in step (7) was changed to 6 mm.
Comparative Example 4.4: Preparation of Bionic Duodenum (without Addition of Silicone Oil)
[0252] On the basis of example 4.1, the diameter of the mould in step (2) was changed to 4 cm, and the length was changed to 30 cm; the diameter of the needle in step (3) was changed to 0.4 mm, and the diameter of the small hole was changed to 0.6 mm; the baking conditions in step (4) were changed to: baking was conducted for 30 min at 130° C.; and silicone oil in step (5) was omitted.
Comparative Example 4.5: Preparation of Bionic Duodenum (with Addition of Glycerinum)
[0253] On the basis of example 4.1, the diameter of the mould in step (2) was changed to 4 cm, and the length was changed to 30 cm; the diameter of the needle in step (3) was changed to 0.4 mm, and the diameter of the small hole was changed to 0.6 mm; the baking conditions in step (4) were changed to: baking was conducted for 30 min at 130° C.; and silicone oil in step (5) was replaced with glycerinum.
Example 4.4: Detection of Bionic Duodenum
[0254] The human duodenum anatomical model, the bionic duodenums prepared in examples 4.1 to 4.3, the bionic duodenums prepared in comparative examples 4.1 to 4.5 and the similar foreign products (Fast 8 model of bionic silica gel duodenums purchased from American Dragon Skin company), which are the same in length, were taken and subjected to detection of intestine area, transparency, hardness, expansion rate and elasticity. The detection results are shown in Table 4.
[0255] It can be seen from Table 4 that the indexes of the bionic duodenums of the disclosure and the true duodenum are relatively close by comparison, and compared with the similar foreign products, the indexes are better. Therefore, the bionic duodenums of the disclosure can replace the true duodenum to predict the live test, and can completely or partially replace the live test, so as to reduce the cost and time, improve the repeatability and accuracy, and there is no theoretical limitation.
TABLE-US-00004 TABLE 4 Performance Detection Results Whether villi have a Trans- function of Intestinal parent Hard- Expan- Elas- secreting area effect ness sion rate ticity intestinal juice Human >3000 cm.sup.2 Opaque 40 22% 250% Yes duodenum anatomical model Example 1 >3000 cm.sup.2 Good 42 22% 240% Yes Example 2 >3000 cm.sup.2 Good 40 25% 280% Yes Example 3 >3000 cm.sup.2 Good 39 23% 250% Yes Comparative 300 cm.sup.2 Good 41 22% 230% No example 1 Comparative >3000 cm.sup.2 Poor, and 39 19% 210% Yes example 2 bubbles exist Comparative >3000 cm.sup.2 Poor 44 23% 260% Yes example 3 Comparative >3000 cm.sup.2 Good 69 10% 530% Yes example 4 Comparative >3000 cm.sup.2 Good 70 12% 450% Yes example 5 Similar foreign 300 cm.sup.2 Good 30 20% 1000% No products
Example 5.1: Preparation of Bionic Jejunum
[0256] (1) Preparation of clay: soft clay was repeatedly kneaded to obtain soft clay having good malleability; [0257] (2) pressing of a jejunum mould: the kneaded soft clay was put into a precise human jejunum anatomical model of a medicine gastroenterology department and strongly squeezed, the human jejunum anatomical model was taken out to obtain the soft clay jejunum mould having the interior physiological structure of a true jejunum, and the mould is 2 cm in diameter and 25 cm in length; [0258] (3) manufacturing of hollow villi: a plurality of needles having a diameter of 0.5 mm were taken and pricked each imprint of the above mould to poke so as to form small holes having a diameter of 1 mm and a depth of 5 mm, and the needles continued to be kept inside the mould; [0259] (4) baking and molding of the jejunum mould: the duodenum mould was put into an oven and baked for 15 minutes at 140° C. so that the duodenum mould was solidified and molded and then naturally cooled, so as to obtain the bionic jejunum mould; [0260] (5) preparation of silica gel: transparent silica gel, silicone oil and a curing agent tetraethoxysilane were placed in a beaker in a ratio of 100:2:2, sufficiently stirred and uniformly mixed; [0261] (6) the uniformly mixed silica gel was put into a vacuum machine, and vacuumized at a negative pressure of 0.09 MPa to remove the bubbles for 5 minutes to obtain bubble-free silica gel; [0262] (7) the bubble-free silica gel was uniformly smeared on the surface of the above bionic duodenum mould, with a thickness of about 1.5 mm; [0263] (8) the uniformly smeared jejunum mould stood for 2 hours so that the mould could be completely solidified and molded, and the needles outside the mould were pulled out to obtain a jejunum silica gel model having intestinal villi and being hollow; [0264] (9) the surface of the jejunum mould in which needles were only pulled out and silica gel does not fall off is covered with oily paper, and a hollow cylinder having a diameter of 2 cm and height of 4 cm was placed outside the mould and well adhered and fixed; [0265] (10) bubble-free silica gel was uniformly smeared in a gap between the oily paper of the jejunum mould and the cylinder, and standing was carried out for 2 h until the silica gel was completely solidified and molded; [0266] (11) the solidified silica gel mould was placed in water for 10 min, and the oily paper was taken out from the hollow cylinder after water softened the oily paper; and [0267] (12) after the silica gel was removed from the jejunum mould, and after certain pruning, the bionic jejunum silica gel model having intestine wall corrugations of the jejunum physiological structure and villi capable of secreting intestinal juice was obtained.
Example 5.2: Preparation of Bionic Jejunum
[0268] On the basis of example 5.1, the diameter of the mould in step (2) was changed to 2.5 cm; the diameter of the needle in step (3) was changed to 0.3 mm, and the diameter of the small hole was changed to 0.5 mm; the baking conditions in step (4) were changed to: baking was carried out for 20 min at 150° C.; the curing agent in step (5) was vinyl triamine, and meanwhile the mass ratio of transparent silica gel to silicone oil to the curing agent was changed to 100:1.5:2; the smearing thickness in step (7) was changed to 2 mm; the standing time in step (8) was changed to 4 h; and the standing time in step (10) was changed to 1 h.
Example 5.3: Preparation of Bionic Jejunum
[0269] On the basis of example 5.1, the diameter of the mould in step (2) was changed to 3 cm, and the length was changed to 30 cm; the diameter of the needle in step (3) was changed to 0.1 mm, and the diameter of the small hole was changed to 0.2 mm; the baking conditions in step (4) were changed to: baking was carried out for 30 min at 130° C.; the curing agent in step (5) was changed to diaminodiphenyl-methane (DDM), and meanwhile the mass ratio of transparent silica gel to silicone oil to the curing agent was changed to 100:2:2.5; the smearing thickness in step (7) was changed to 2.5 mm; the standing time in step (8) was changed to 1 h; and the standing time in step (10) was changed to 1 h.
Comparative Example 5.1: Preparation of Bionic Duodenum (without Villi)
[0270] On the basis of example 5.1, the diameter of the mould in step (2) was changed to 2.5 cm, and the length was changed to 30 cm; step (3) was omitted; the baking conditions in step (4) were changed to: baking was conducted for 30 min at 130° C.; the mass ratio of transparent silica gel to silicone oil to the curing agent in step (5) was changed to 100:1.5:2.5; the smearing thickness in step (7) was changed to 2 mm; step (8) was changed to: the uniformly smeared jejunum mould stood for 1 h so that it was completely solidified and molded; and steps (9) to (11) were omitted.
Comparative Example 5.2: Preparation of Bionic Jejunum (Silica Gel is not Vacuumized after Mixing)
[0271] On the basis of example 5.1, the diameter of the mould in step (2) was changed to 2.5 cm, and the length was changed to 30 cm; the diameter of the needle in step (3) was changed to 0.2 mm, and the diameter of the small hole was changed to 0.5 mm; the baking conditions in step (4) were changed to: baking was conducted for 20 min at 140° C.; the mass ratio of transparent silica gel to silicone oil to the curing agent in step (5) was changed to 100:2.5:1.5; step (6) was omitted; and the smearing thickness in step (7) was changed to 2 mm.
Comparative Example 5.3: Preparation of Bionic Jejunum (the Thickness of the Smeared Silica Gel is Increased)
[0272] On the basis of example 5.1, the diameter of the mould in step (2) was changed to 2.5 cm, and the length was changed to 30 cm; the diameter of the needle in step (3) was changed to 0.4 mm, and the diameter of the small hole was changed to 0.6 mm; the baking conditions in step (4) were changed to: baking was conducted for 30 min at 130° C.; the mass ratio of transparent silica gel to silicone oil to the curing agent in step (5) was changed to 100:2:2; and the smearing thickness in step (7) was changed to 6 mm.
Comparative Example 5.4: Preparation of Bionic Jejunum (without Addition of Silicone Oil)
[0273] On the basis of example 5.1, the diameter of the mould in step (2) was changed to 2.5 cm, and the length was changed to 30 cm; the diameter of the needle in step (3) was changed to 0.4 mm, and the diameter of the small hole was changed to 0.6 mm; the baking conditions in step (4) were changed to: baking was conducted for 30 min at 130° C.; and silicone oil in step (5) was omitted.
Comparative Example 5.5: Preparation of Bionic Jejunum (with Addition of Glycerinum)
[0274] On the basis of example 5.1, the diameter of the mould in step (2) was changed to 2.5 cm, and the length was changed to 30 cm; the diameter of the needle in step (3) was changed to 0.4 mm, and the diameter of the small hole was changed to 0.6 mm; the baking conditions in step (4) were changed to: baking was conducted for 30 min at 130° C.; and silicone oil in step (5) was replaced with glycerinum.
Example 5.4: Detection of Bionic Jejunum
[0275] The human jejunum anatomical model, the bionic jejuna prepared in examples 5.1 to 5.3, the bionic jejuna prepared in comparative examples 5.1 to 5.5 and the similar foreign products (Fast 4 model of bionic silica gel jejuna purchased from American Dragon Skin company), which are the same in length, were taken and subjected to detection of intestine area, transparency, hardness, expansion rate and elasticity. The detection results are shown in Table 5.
[0276] It can be seen from Table 5 that the indexes of the bionic jejuna of the disclosure and the true jejunum are relatively close by comparison, and compared with the similar foreign products, the indexes are better. Therefore, the bionic jejuna of the disclosure can replace the true jejunum to predict the live test, and can completely or partially replace the live test, so as to reduce the cost and time, improve the repeatability and accuracy, and there is no theoretical limitation.
TABLE-US-00005 TABLE 5 Performance Detection Results Whether villi have a function of Intestinal Transparent Hard- Expan- Elas- secreting area effect ness sion rate ticity intestinal juice Human jejunum >4000 cm.sup.2 Opaque 36 25% 240% Yes anatomical model Example 1 >4000 cm.sup.2 Good 36 26% 260% Yes Example 2 >4000 cm.sup.2 Good 35 24% 230% Yes Example 3 >4000 cm.sup.2 Good 38 25% 220% Yes Comparative 300 cm.sup.2 Good 39 24% 210% No example 1 Comparative >4000 cm.sup.2 Poor, and 33 26% 240% Yes example 2 bubbles exist Comparative >4000 cm.sup.2 Poor 36 25% 250% Yes example 3 Comparative >4000 cm.sup.2 Good 60 12% 540% Yes example 4 Comparative >4000 cm.sup.2 Good 70 15% 490% Yes example 5 Similar foreign 300 cm.sup.2 Good 30 10% 1000% No products
[0277] Although the disclosure has been disclosed by preferred examples as above, but the preferred examples are not intended to limit the disclosure, those skilled in the art can make various variations and modifications without departing from the spirit and scope of the disclosure, and therefore the protective scope of the disclosure should be based on claims.