New application of galactooligosaccharide
By adding galactose oligosaccharides to the mice's diet, it uses its influence on intestinal flora and bile acid metabolism to inhibit the formation of gallbladder stones, solving the problem of prevention of gallbladder stones and achieving a significant reduction in the incidence of stones.
Patent Information
- Application Number
- CN202311719583.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-12-14
- Publication Date
- 2025-07-29
AI Technical Summary
The formation mechanism of gallbladder stones in the prior art has not been effectively prevented, especially the high incidence of steroid stones poses a great threat to patients' health, and there are limitations in the treatment methods based on surgical methods.
By adding galactose oligosaccharides to the mouse diet, using its effect on intestinal flora and bile acid metabolism, the formation of gallbladder stones was inhibited. The specific method included changing 6% galactose oligosaccharide solution as drinking water in the stone model group.
The significant reduction in the rate of gallbladder stone formation from 6/12 to 2/12 provides new ideas for preventing stone occurrence, indicating the potential role of galactose oligosaccharide in diet regulation.
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Figure CN120381453A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of pharmaceutical technology, and specifically to a new use of galactooligosaccharides. Background Art
[0002] Gallbladder stones are a common disease in the digestive system. The incidence rate in the adult population in China can reach (10 - 15)%, and the current treatment is mainly surgical, so the disease burden is heavy and the health threat is great. 90% of gallbladder stones in China are cholesterol stones. Bile is mainly composed of cholesterol, bile acids and phospholipids, and the supersaturation of cholesterol in bile is a prerequisite for the formation of cholesterol stones. Under normal physiological conditions, bile acids and phospholipids form mixed micelles to promote the dissolution of hydrophobic cholesterol. However, when cholesterol secretion is excessive, bile acids or phospholipids are lacking, or hydrophobic bile acids increase, the homeostasis of cholesterol in bile may be disrupted, leading to its supersaturation and precipitation, and then the formation of cholesterol stones. Current research has proved that the gut microbiota plays an important role in the pathogenesis of stones based on its significant influence on bile acid metabolism.
[0003] Galactooligosaccharides are an important class of dietary prebiotics. Multiple studies have shown that galactooligosaccharides can have a significant impact on the gut microbiota and bile acid metabolism, and then have a certain effect on some lipid metabolism disorder-related diseases such as non-alcoholic fatty liver, hyperlipidemia, and hypercholesterolemia. As a common disease closely related to lipid metabolism, gallbladder stones may also be affected by galactooligosaccharides. Therefore, we conducted a series of experiments to explore the relationship between the two. Summary of the Invention
[0004] The present invention provides a new use of galactooligosaccharides that can inhibit the formation of gallbladder stones, providing a new idea for preventing the occurrence of stones.
[0005] The technical solution adopted by the present invention is: a new use of galactooligosaccharides, inhibiting the formation of gallbladder stones.
[0006] The molecular structure of the galactooligosaccharides contains 1 - 7 galactosyl groups.
[0007] As a further scheme of the present invention: the specific experimental method is as follows:
[0008] Main reagents and materials: galactooligosaccharides; mouse stone model feed.
[0009] Source of experimental animals: Animal breed and strain: mouse, C57BL / 6J; Gender: male; Week age: 4 weeks old; Body weight: 16 - 20 g.
[0010] Experimental environment: Raised in an SPF environment, with the breeding conditions being a room temperature of 20 - 26°C; relative humidity of 40 - 70%; automatic lighting with a 12-hour light-dark cycle; the standards of the experimental animal house comply with the national standard GB14925 - 2010 of the People's Republic of China; drinking water: RO membrane reverse osmosis sterile water. The breeding density is defaulted to 4 mice per cage, and the bedding is changed once a week.
[0011] Experimental procedure: All mice started the experiment after being experimentally raised for one week. 36 male C57BL / 6J mice at 5 weeks of age were randomly divided into 3 groups of 12 each, namely: blank group, simple calculus model group, galactooligosaccharide + calculus model group. The galactooligosaccharide solution was changed once a day.
[0012] From the start of the experiment, the body weight of the mice was measured every three days, and a body weight curve was plotted to observe whether there were significant changes in body weight and whether there were significant differences in body weight among the groups. The food and drinking water intakes of the experimental group and the control group were monitored once a day to determine whether there were significant differences. After abdominal hair removal in the fourth week, B-ultrasound was performed on the mice to determine the calculus formation situation, and then the mice were sacrificed to collect samples for subsequent detection.
[0013] As a further aspect of the present invention: The mice need to be adaptively fed for 7 days before the experiment. Healthy animals are selected as the test animals, and they are randomly grouped according to body weight. After grouping, a unique and permanent animal number is assigned to each animal.
[0014] As a further aspect of the present invention: The 12-hour light-dark cycle is to turn on the light at 07:00 and turn off the light at 19:00.
[0015] As a further aspect of the present invention: The average body weight of male C57BL / 6J mice at 5 weeks of age is about 18 to 22 g.
[0016] As a further aspect of the present invention: The blank group is given normal growth and reproduction feed and normal drinking water; the simple calculus model group is given calculus model feed and normal drinking water; the galactooligosaccharide + calculus model group is given calculus model feed, and the normal drinking water is replaced with a 6% galactooligosaccharide solution for free drinking.
[0017] Advantages of the present invention:
[0018] The present invention discovers a new use of galactooligosaccharide, which can inhibit the formation of gallstones. C57 / BL6J mice of the same batch were raised under the same conditions. At the fourth week, the calculus formation rate of the mice only given calculus model feed was 6 / 12, while the calculus formation rate of the mice given both calculus model feed and galactooligosaccharide was only 2 / 12. This discovery provides a new idea for preventing the occurrence of stones, that is, controlling the occurrence of stones by adding dietary probiotics or changing the diet pattern. Description of the drawings
[0019] Figure 1 Incidence of gallbladder stones in C57BL / 6J mice in the simple stone model group for the new use of galactooligosaccharides of the present invention after 4 weeks of feeding, and B-ultrasound result diagram of 6 / 12.
[0020] Figure 2 Incidence of gallbladder stones in C57BL / 6J mice in the galactooligosaccharides + stone model group for the new use of galactooligosaccharides of the present invention after 4 weeks of feeding, and B-ultrasound result diagram of 2 / 12.
[0021] Figure 3 Incidence of gallbladder stones in C57BL / 6J mice in the simple stone model group for the new use of galactooligosaccharides of the present invention after 4 weeks of feeding, and final dissection result diagram of 6 / 12.
[0022] Figure 4 Incidence of gallbladder stones in C57BL / 6J mice in the galactooligosaccharides + stone model group for the new use of galactooligosaccharides of the present invention after 4 weeks of feeding, and final dissection result diagram of 2 / 12. Detailed implementation manners
[0023] The present invention will be further described below.
[0024] New use of galactooligosaccharides, inhibiting the formation of gallbladder stones.
[0025] The specific experimental method is as follows:
[0026] Main reagents and materials: Galactooligosaccharides (purchased from Shanghai Yuanye Bio-Technology Co., Ltd., S11138). Mouse stone model feed (purchased from Nantong TROPHY Feed Technology Co., Ltd., TP28900).
[0027] Source of experimental animals: Jiangsu Jicui Yakang Laboratory Animal Technology Co., Ltd., animal breed and strain: mouse, C57BL / 6J; gender: male; age: 4 weeks old; weight: 16 - 20 g. Before the experiment, the animals need to be adaptively fed for 7 days. Healthy animals are selected as the test animals. They are randomly grouped according to their weights. After grouping, each animal is assigned a unique and permanent animal number.
[0028] Experimental environment: Raised in a SPF environment, the breeding conditions are room temperature 20 - 26 °C; relative humidity 40 - 70%; automatic lighting, 12 h light and dark alternation (lights on at 07:00 and lights off at 19:00); the standards of the test animal house comply with the national standard GB14925 - 2010 of the People's Republic of China; drinking water: RO membrane reverse osmosis sterile water. The breeding density is defaulted to 4 animals / cage, and the bedding is changed once a week.
[0029] Experimental procedure: All mice were experimentally raised for one week before the experiment began. Thirty-six 5-week-old male C57BL / 6J mice (average body weight about 18 to 22 g) were randomly divided into 3 groups of 12 each, namely: blank group (fed with normal growth and reproduction feed and given normal drinking water), simple stone model group (fed with stone model feed and given normal drinking water), and galactooligosaccharide + stone model group (fed with stone model feed, and the normal drinking water was replaced with a 6% galactooligosaccharide solution for free drinking). The galactooligosaccharide solution was changed once a day.
[0030] From the start of the experiment, the body weight of the mice was measured every three days, and a body weight curve was plotted to observe whether there were significant changes in body weight and whether there were significant differences in body weight among the groups. The food and water intake of the experimental group and the control group were monitored once a day to determine whether there were significant differences. After abdominal hair removal in the fourth week, B-ultrasound of the mice was performed to determine the stone formation situation, and then the mice were sacrificed to collect samples for subsequent detection.
[0031] The present invention discovers a new use of galactooligosaccharide, which can inhibit the formation of gallstones. C57 / BL6J mice of the same batch were raised under the same conditions. In the fourth week, the stone formation rate of the mice fed only with the stone model feed was 6 / 12, while the stone formation rate of the mice fed with the stone model feed and galactooligosaccharide was only 2 / 12. This discovery provides a new idea for preventing stone formation, that is, controlling the occurrence of stones by adding dietary probiotics or changing the diet pattern.
[0032] The present invention also provides a galactooligosaccharide solution, which catalyzes lactose by a biological enzyme method to obtain a mixed solution. The mixed solution is ultrafiltered through a ceramic membrane with a pore size of 0.1 m and adsorbed by activated carbon to obtain a galactooligosaccharide mixed solution. The biological enzyme is β-galactosidase, and the addition amount of the enzyme is 50 U / g of lactose dry basis. The enzyme reaction conditions are that the lactose concentration is 45%, the reaction temperature is 50 °C, and the reaction pH is 5.5.
[0033] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that: they can still modify the technical solutions recorded in the foregoing embodiments, or perform equivalent replacements on some of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.
Claims
1. Use of galactooligosaccharides in inhibiting gallstones.
2. The use according to claim 1, wherein, The molecular structure of the galactooligosaccharides contains 1-7 galactosyl groups.
3. The new use of the galactooligosaccharides according to claim 1, characterized in that: The specific experimental method is as follows: Main reagents and materials: Galactooligosaccharides; Mouse stone model feed; Source of experimental animals: Animal breed and strain: Mouse, C57BL / 6J; Gender: Male; Week age: 4 weeks old; Body weight: 16-20 g; Experimental environment: Raised in SPF environment, the breeding conditions are room temperature 20-26 °C; Relative humidity 40-70%; Automatic lighting, 12 h light and dark alternation; Drinking water: RO membrane reverse osmosis sterile water; Breeding density is default 4 per cage, and the bedding is changed once a week; Experimental process: After all mice are experimentally raised for one week, the experiment starts. 36 male C57BL / 6J mice at 5 weeks old are randomly divided into 3 groups with 12 mice in each group, namely: blank group, simple stone model group, galactooligosaccharides + stone model group, and the galactooligosaccharides solution is changed once a day; From the start of the experiment, the body weight of the mice is measured every three days, and the body weight curve is drawn to observe whether there are obvious changes in body weight and whether there are obvious differences in body weight among groups. The food and drinking water intake of the experimental group and the control group are monitored once a day to judge whether there are obvious differences; After abdominal hair removal in the fourth week, B-ultrasound of the mice is performed to judge the stone formation situation, and then the mice are sacrificed to collect samples for subsequent detection.
4. The new use of galactooligosaccharide according to claim 3, characterized in that: The mice need to be adaptively fed for 7 days before the experiment. Healthy animals are selected as test animals and randomly grouped according to body weight. After grouping, a unique and permanent animal number is assigned to each animal.
5. The new use of galactooligosaccharides according to claim 3, characterized in that: The 12 h light and dark alternation is to turn on the light at 07:00 and turn off the light at 19:
00.
6. The new use of galactooligosaccharide according to claim 3, characterized in that: The average body weight of the male C57BL / 6J mice at 5 weeks old is about 18 to 22 g.
7. The new use of galactooligosaccharides according to claim 3, characterized in that: The blank group is given normal growth and reproduction feed and normal drinking water; The simple stone model group is given stone model feed and normal drinking water; The galactooligosaccharides + stone model group is given stone model feed, and the normal drinking water is replaced with 6% galactooligosaccharides solution for free drinking.
8. A method for preparing a galactooligosaccharide solution, characterized in that: The lactose is catalyzed by the biological enzyme method to obtain a mixed solution. The mixed solution is ultrafiltered through a 0.1 m pore size ceramic membrane and adsorbed by activated carbon to obtain a galactooligosaccharides mixed solution. The biological enzyme is β-galactosidase, and the addition amount of the enzyme is 50 U / g lactose dry basis. The enzyme reaction conditions are that the lactose concentration is 45%, the reaction temperature is 50 to 60 °C, and the reaction pH is 5.5.