CN111568949A - Application of mulberry extract in preparation of medicine for regulating animal intestinal flora - Google Patents
Application of mulberry extract in preparation of medicine for regulating animal intestinal flora Download PDFInfo
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- CN111568949A CN111568949A CN202010492850.3A CN202010492850A CN111568949A CN 111568949 A CN111568949 A CN 111568949A CN 202010492850 A CN202010492850 A CN 202010492850A CN 111568949 A CN111568949 A CN 111568949A
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Abstract
The invention relates to application of a mulberry extract in preparing a medicament for regulating animal intestinal flora, which is characterized in that the mulberry extract is prepared according to the following steps: step 1): preparing a crude extract; step 2): separation on a cationic resin and/or optionally an anionic resin; step 3): carrying out alcohol precipitation treatment on the resin effluent liquid in the step 2); optional step 4) concentration and drying treatment. The extract can reduce the abundance of harmful bacteria of Lactobacillaceae, Ruminoccaceae, Rikenella ceae, Aerococcus, Desulfovibrionaceae, Corynebacteriaceae, Enterococcaceae and Christenselliacea, increase the abundance of beneficial bacteria of Bacteroidaceae, Vellonellaceae, Erysipellicaceae, Vercomicrobiaceae and Lachnospiraceae, has better treatment effect on intestinal flora imbalance related diseases, and has high safety and low production cost.
Description
Technical Field
The invention relates to application of a mulberry extract in preparing a medicament for regulating animal intestinal flora.
Background
There is a large number of normal microflora, i.e. the intestinal flora, in the human intestine. The intestinal flora is the most complex microecosystem with the largest flora variety and quantity in human body, and the variety is more than 1000, and the quantity is about 10 times of the total number of human cells. The intestinal microorganisms participate in the physiological activities of the organism such as substance metabolism, nutrient absorption and synthesis and the like, maintain the normal physiological activities of the human body such as immunity, metabolism and the like, and establish a mutual and reciprocal symbiotic relationship with the human body. Studies have shown that gut flora may influence host health by regulating body weight, bile acid metabolism, pro-inflammatory activity, insulin sensitivity and gut hormone release. Changes in dietary structure, diseases, improper use of drugs, etc. all cause imbalance of intestinal flora, thereby posing a threat to human health. Therefore, in recent years, there are many reports of studies on the regulation of intestinal flora. Wherein, the research report about diabetes and intestinal flora shows that the intestinal flora is closely related to the II type diabetes, can induce human body to generate a plurality of mechanisms by participating in the synthesis of short-chain fatty acid, lipopolysaccharide, bile acid, angiopoietin-like protein and the like, therefore, the damage and the apoptosis of insulin beta cells are caused, the sensitivity of human bodies to insulin is reduced (Gunn, Yan Korea, the research progress of the correlation between the intestinal flora and the type 2 diabetes [ J ] medical review, 2019(10): 2034-2038.), the application of the sargassum graminifolium polysaccharide extract in regulating the intestinal flora and further preventing the diabetes is researched by Zhangyan and the like (Zhangyan, Miao Shing, Wu Wen, Wang Xiao Yu, the application of the sargassum graminifolium polysaccharide extract in improving the intestinal flora and preventing the diabetes is China, 1510237905.5[ P ] 2015-05-12).
Currently, there are few drugs on the market for diabetes-related disorders of the intestinal flora, and therefore, there is a need to develop more effective drugs to better treat the related diseases.
Disclosure of Invention
In view of the above problems, the present invention provides a method for regulating intestinal flora, and more particularly, the present invention provides a use of mulberry extract for regulating intestinal flora in animals, wherein the mulberry extract is prepared according to the following steps: step 1): preparing a crude extract; step 2): separation on a cationic resin and/or optionally an anionic resin; step 3): carrying out alcohol precipitation treatment on the resin effluent liquid in the step 2); optional step 4) concentration and drying treatment.
In one embodiment of the present invention, the mulberry extract comprises alkaloids, polysaccharides, flavones and amino acids. Preferably, the alkaloids comprise DNJ (1-deoxynojirimycin ) and FAG (Fagomine).
In one embodiment of the invention, said modulation of the intestinal flora comprises modulating the flora composition of the intestinal flora. Preferably, said modulation of the intestinal flora comprises decreasing the abundance of Lactobacillaceae, Ruminoccaceae, Rakennellaceae, Aerococcaceae, Desulfovibrio viridae, Corynebacteriaceae, Enterococcaceae, and Christensellaceae, increasing the abundance of Bacteroidaceae, Veillonellidae, Erysipellotrichaceae, Vercomicrobiaceae, Lachnospiraceae. Preferably, the Lactobacillaceae family includes Lactobacillus, the Phycomaceae family includes Alisiples, the Aerococcaceae family includes Aerococcus, the Desulfovibrio family includes Desulfovibrio, the Corynebacteriaceae family includes Corynebacterium, the Enterococcus may include Enterococcus, the Bacteroides family includes Bacteroides, the Roveomycetaceae family includes Allobacillus and Faecalibacillus, the Lachnospiriceae family Lachnospiraceae includes Lachnocrostinium. Research shows that the bacteroides in the strains are short-chain fatty acid SCFA producing strains and can stimulate the secretion of a G protein receptor and GLP-1; verrucomicrobia can reduce LPS levels and are generally considered as potential weight-reducing bacteria; faecalibaculum, a short chain fatty acid (butyric acid) producing bacterium; allobaculum has potential benefits on host physiology; inhibiting proliferation of Lissajous bacteria, and inhibiting diabetes; the desulfurization vibrio belongs to sulfate reducing bacteria, sulfate can be reduced into sulfide by the sulfate reducing bacteria in an intestinal tract, the sulfide has a toxic effect on intestinal epithelial cells, abnormal proliferation and metabolism of the epithelial cells can be induced, so that the intestinal barrier function is damaged, the proliferation of the desulfurization vibrio is inhibited, the intestinal barrier function can be improved, the intestinal permeability is reduced, and the enterogenic endotoxemia is reduced.
In one embodiment of the invention, the animal is a mammal, including humans and rodents. Preferably, the animal glycolipid metabolism is abnormal. More preferably, the animal is a human or a mouse.
The extract of Moraceae of the present invention has a regulating effect on the composition of intestinal flora of animals, especially the intestinal flora of animals with abnormal glycolipid metabolism.
In one embodiment of the present invention, the medicament further comprises a pharmaceutically acceptable carrier. The carrier is an inactive component which has no toxic action on human body and accords with the medication route or the administration mode. The carrier may be a solid or liquid vehicle. Solid excipients, for example, include microcrystalline cellulose, mannitol, lactose, pregelatinized starch, low-substituted hydroxypropyl cellulose, crospovidone, sodium carboxymethyl starch, aspartame, calcium hydrogen phosphate, soybean oil, medium chain oil, cholesterol, soy lecithin, sodium lactate, poloxamer, sodium lauryl sulfate, sodium carboxymethyl cellulose, gelatin, xanthan gum, povidone, starch, magnesium stearate, sodium carboxymethyl starch, and talc; liquid excipients include, for example, water, ethanol, syrup, and glycerol.
In one embodiment of the invention, the medicament further comprises a therapeutically effective amount of at least one therapeutic agent or composition selected from the group consisting of: bifidobacteria, lactobacillin and enteritis tablet.
In one embodiment of the invention, the medicament is administered orally. Preferably, the pharmaceutical is in a dosage form selected from the group consisting of capsules, tablets, oral solutions, oral emulsions, pills, granules, syrups and powders.
Drawings
FIG. 1 isA specific parameter index for analysis of intestinal microbial diversity in KKAY mice by SZ-A long-term administration (A) OTU number (B) Shannon index based on OTU analysis (C) Chao index based on OTU analysis (D) PCoA analysis. DM, model control, SZAH, treatment group.
FIG. 2 shows the effect of SZ-A on the composition of the microbial community of the KKAY mouse intestinal microbial diversity after long-term administration (A) differential analysis of colony formation at the family level (family level Wilcox rank sum test) (B) differential analysis of colony formation at the genus level (genus level Wilcox rank sum test). CON, control, SZA, treatment.
Detailed Description
The following examples and test examples are illustrative only and are not to be construed as limiting the invention. In addition, the technical features related to the different embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
The contents of the components involved in the present invention were measured according to a known method (see methods described in patent publication Nos. CN111077247A and CN 110393738A).
Preparation example 1
Pulverizing fresh ramulus Mori (11 # Yue Mulberry), adding 4000L water, extracting for 2 hr under reflux, mixing extractive solutions, and filtering to remove insoluble substances to obtain crude extractive solution. And (3) carrying out heat concentration on the crude extract until the solid content reaches 4%, and using the crude extract as a sample loading solution of a cation resin column.
Loading 150kg of D113 type macroporous weakly acidic styrene series cationic resin into a column, and washing with 2mol/L hydrochloric acid solution until the pH of eluate is 4.5; washing with 1mol/L sodium hydroxide solution until the pH of the eluate is 8.5; washing with 2mol/L hydrochloric acid solution until the pH of an eluate is 4.5; and then washed with 5 column volumes of deionized water to complete the activation. And (3) loading the concentrated extracting solution, eluting by using 1000L of 2.5mol/L ammonia water at the elution speed of 6BV/h, collecting the eluent when the pH of the effluent of the cation column is detected to be more than 7, stopping collecting when the collected liquid reaches 900L, and directly purifying the collected liquid by using an anion column.
Loading 400kg of D218 macroporous strongly basic acrylic acid series anionic resin into a column, and washing by using 1.5mol/L sodium hydroxide solution until the pH of an eluate is 9.0; washing with 1.5mol/L hydrochloric acid solution until the pH of the eluate is 3.5; washing with 1.5mol/L sodium hydroxide solution until the pH of the eluate is 9.0; and (4) completing activation. And loading the collected cation resin eluent to anion resin, and collecting the effluent until the effluent reaches 870L.
And (3) filtering the collected liquid obtained after the anion column separation by using a microfiltration membrane to remove impurities, concentrating by using a counter ion permeable membrane, transferring the concentrated liquid into an alcohol precipitation tank, wherein the specific gravity of the concentrated liquid is 1.1, and adding 15kg of absolute ethyl alcohol into the alcohol precipitation tank at the speed of 400rpm of a stirring paddle. Stopping stirring after the ethanol is added, precipitating with ethanol for 24h, collecting supernatant, and concentrating under reduced pressure to obtain ramulus Mori extract. In addition, fresh cortex Mori and folium Mori (Yue Mulberry No. 11) are extracted, and the extraction method and parameters are the same as above.
In the obtained ramulus Mori extract, alkaloid content is 75%, polysaccharide content is 15%, flavone content is 0.7%, and amino acid content is 5%; the alkaloid contains DNJ (1-deoxynojirimycin ), FAG (Fagomine) and DAB (1, 4-dideoxy-1,4-imino-D-arabinitol, 1,4-dideoxy-1, 4-imino-D-arabinitol), wherein the content of DNJ is 72%.
In the obtained extract of cortex Mori extract, alkaloid content is 67%, polysaccharide content is 20%, flavone content is 0.8%, and amino acid content is 6%; DNJ, FAG and DAB are contained in the alkaloid, wherein the content of DNJ is 70%.
In the obtained mulberry leaf extract, the content of alkaloid is 50%, the content of polysaccharide is 27%, the content of flavone is 3% and the content of amino acid is 16%; DNJ, FAG and DAB are contained in the alkaloid, wherein the content of DNJ is 66%.
Preparation example 2
Pulverizing fresh ramulus Mori (Morus alba L. Ex Fr.2) 10kg, adding 150L water, adding into the pulverized ramulus Mori 2L water, decocting for 3 hr each time, mixing extractive solutions, and filtering to remove insoluble substances. The extract was concentrated by heating until the solid content reached 8%, and transferred to an alcohol precipitation tank, where 2367.9g of absolute ethanol (3L) was added under 300rpm of a stirring paddle. And stopping stirring after the ethanol is added, precipitating with ethanol for 24h, and taking the supernatant as a sample loading solution of the cationic resin column. The cationic resin was activated in the same manner as in example 3 using 002SC type strongly acidic styrene type cationic resin 5kg packed in a column. Sampling the extract subjected to concentration and alcohol precipitation, eluting with 100L of 5mol/L potassium chloride at the elution speed of 5BV/h, detecting the effluent with 20% silicotungstic acid, starting collection when white precipitate is generated, stopping collection when the volume of the collected liquid reaches 25L, and purifying the collected liquid directly through an anion column.
The anion resin was activated in the same manner as in example 3 by using 10kg of type 711 strongly basic styrene anion resin packed in a column. Loading the collected cation resin eluent to anion resin, and collecting the effluent until the effluent reaches
15L ends. The collected solution was re-loaded onto the cationic resin and re-separated twice with the cationic resin and the anionic resin in this order as described above.
And (3) centrifuging the collected liquid obtained after the three-time column separation to remove impurities, concentrating the collected liquid by a counter ion permeable membrane, transferring the concentrated liquid into an alcohol precipitation tank, and adding 125g of absolute ethyl alcohol into the alcohol precipitation tank at the speed of 1000rpm of a stirring paddle. Stopping stirring after the ethanol is added, precipitating with ethanol for 24h, collecting supernatant, and concentrating under reduced pressure to obtain extract. In addition, fresh cortex Mori and folium Mori (SANTOU No. 2) are extracted, and the extraction method and parameters are the same as above.
In the obtained ramulus Mori extract, alkaloid content is 98%, polysaccharide content is 0.2%, and flavone content is 0.05%; DNJ, FAG and DAB are contained in the alkaloid, wherein the content of DNJ is 99 percent.
In the obtained cortex Mori extract, alkaloid content is 95%, polysaccharide content is 2%, flavone content is 0.1%, and amino acid content is 1%; DNJ, FAG and DAB are contained in the alkaloid, wherein the content of DNJ is 96 percent.
In the obtained mulberry leaf extract, the content of alkaloid is 90%, the content of polysaccharide is 4%, the content of flavone is 0.1%, and the content of amino acid is 3%; DNJ, FAG and DAB are contained in the alkaloid, wherein the content of DNJ is 91%.
Preparation example 3
Pulverizing fresh Mori fructus (white mulberry fruit) 100g, adding 300ml alcohol water, adding for 2 times, and extracting under reflux each time
And (3) combining the extracting solutions, and filtering to remove insoluble substances to obtain a crude extracting solution. The crude extract is thermally concentrated until the solid content reaches 2%, and is used as a sample loading liquid of a cation resin column at the temperature of 25 ℃.
Column packing with 732 type strongly acidic styrene cation resin 5g, washing with 2.5mol/L hydrochloric acid solution
The pH of the effluent is 3.5; washing with 1.5mol/L sodium hydroxide solution until the pH of the eluate is 8.0; washing with 2.5mol/L hydrochloric acid solution until the pH of an eluate is 3.5; then, the column was washed with 3 column volumes of deionized water to complete the activation. And (3) loading the concentrated extracting solution, eluting with 3L of 0.1mol/L ammonia water at the elution speed of 10BV/h, collecting the eluent when the pH of the effluent of the cation column is detected to be more than 7, stopping collecting when the collected liquid reaches 1L, and directly purifying the collected liquid through an anion column.
Loading 1.25g of D218 macroporous strongly basic acrylic acid series anion resin into a column, and washing by using 1.5mol/L sodium hydroxide solution until the pH value of an eluate is 9.0; washing with 1.5mol/L hydrochloric acid solution until the pH of the eluate is 3.5; washing with 1.5mol/L sodium hydroxide solution until the pH of the eluate is 9.0; and (4) completing activation. And (4) loading the collected cation resin eluent to anion resin, and collecting the effluent until the effluent reaches 1L.
And (3) centrifuging the collected liquid obtained after the anion column separation to remove impurities, concentrating the collected liquid through a counter ion permeable membrane, transferring the concentrated liquid into an alcohol precipitation tank, and adding 25g of absolute ethyl alcohol into the alcohol precipitation tank at the speed of 100rpm of a stirring paddle. Ethanol
Stopping stirring after the addition, precipitating with ethanol for 24 hr, collecting supernatant, and vacuum drying to obtain extract. Extracting fresh ramulus Mori, cortex Mori, and folium Mori (white mulberry), with the same extraction method and parameters as above.
In the obtained mulberry extract, the content of alkaloid is 45%, the content of polysaccharide is 28%, the content of flavone is 5%, and the content of amino acid is 20%; DNJ, FAG and DAB are contained in the alkaloid, wherein the content of DNJ is 60 percent.
In the obtained ramulus Mori extract, alkaloid content is 48%, polysaccharide content is 25%, flavone content is 4%, and amino acid content is 17%; DNJ, FAG and DAB are contained in the alkaloid, wherein the content of DNJ is 62%.
In the obtained cortex Mori extract, alkaloid content is 45%, polysaccharide content is 27%, flavone content is 6%, and amino acid content is 18%; DNJ, FAG and DAB are contained in the alkaloid, wherein the content of DNJ is 61%.
In the obtained mulberry leaf extract, the content of alkaloid is 30%, the content of polysaccharide is 34%, the content of flavone is 7% and the content of amino acid is 30%; DNJ, FAG and DAB are contained in the alkaloid, wherein the content of DNJ is 55 percent.
Preparation example 4
Pulverizing fresh ramulus Mori (ramulus Mori in Guangdong), adding 11500L water, heating and reflux-extracting for 2 hr, mixing extractive solutions, and filtering to remove insoluble substances to obtain crude extractive solution. The crude extract is centrifuged to remove impurities and then concentrated by a counter ion permeable membrane to solid
The content reaches 1 percent, and the product is used as the sample loading solution of the cation resin column.
150kg of D001 type macroporous strongly acidic styrene cationic resin was packed in a column, and the column was treated in the same manner as in preparation example 1
The cationic resin is activated. And (3) loading the concentrated crude extract, eluting with 5000L of 0.04mol/L ammonium nitrate at an elution speed of 5BV/h, detecting the effluent with 20% silicotungstic acid, starting to collect when a white precipitate is generated, and stopping collecting when the collected liquid reaches 1000L.
And (3) concentrating the collected liquid obtained after the separation of the cation column by using a nanofiltration membrane, transferring the concentrated liquid with the specific weight of 1.3 into an alcohol precipitation tank, and adding 1.7kg of absolute ethyl alcohol into the alcohol precipitation tank under the stirring speed of 600 rpm. Stopping stirring after the ethanol is added, precipitating with ethanol for 24h, collecting supernatant, and concentrating under reduced pressure to obtain extract. In addition, fresh cortex Mori and folium Mori (Guangdong mulberry) are extracted by the same method and parameters as above.
In the obtained ramulus Mori extract, alkaloid content is 15%, polysaccharide content is 40%, flavone content is 0.7%, and amino acid content is 40%; DNJ, FAG and DAB are contained in the alkaloid, wherein the content of DNJ is 55 percent.
In the obtained cortex Mori extract, alkaloid content is 10%, polysaccharide content is 42%, flavone content is 0.8%, and amino acid content is 41%; DNJ, FAG and DAB are contained in the alkaloid, wherein the content of DNJ is 50%.
In the obtained mulberry leaf extract, the content of alkaloid is 8%, the content of polysaccharide is 45%, the content of flavone is 0.6%, and the content of amino acid is 43%; DNJ, FAG and DAB are contained in the alkaloid, wherein the content of DNJ is 49 percent.
Preparation example 5
Taking 333kg of dry ramulus Mori (Yue Mulberry No. 11), pulverizing, adding 4000L of water, extracting by heating reflux method twice, refluxing for 1 hr each time, mixing extractive solutions, filtering, and concentrating the extractive solution to 1kg crude drug amount/L.
Loading 150kg of D113 type macroporous weakly acidic styrene series cationic resin into a column, and washing with 2mol/L hydrochloric acid solution until the pH of eluate is 4.5; washing with 1mol/L sodium hydroxide solution until the pH of the eluate is 8.5; washing with 2mol/L hydrochloric acid solution until the pH of an eluate is 4.5; and then washed with 5 column volumes of deionized water to complete the activation. And (3) loading the concentrated extracting solution, eluting by using 1000L of 2.5mol/L ammonia water at the elution speed of 6BV/h, collecting the eluent when the pH of the effluent of the cation column is detected to be more than 7, stopping collecting when the collected liquid reaches 900L, and directly purifying the collected liquid by using an anion column.
Loading 62.5kg of D218 macroporous strongly basic acrylic acid series anion resin into a column, and washing by using 1.5mol/L sodium hydroxide solution until the pH value of an eluate is 9.0; washing with 1.5mol/L hydrochloric acid solution until the pH of the eluate is 3.5; washing with 1.5mol/L sodium hydroxide solution until the pH of the eluate is 9.0; and (4) completing activation. And loading the collected cation resin eluent to anion resin, and collecting the effluent with the pH value of more than 8 until the effluent reaches 870L.
And (3) filtering the collected liquid obtained after the anion column separation by using a microfiltration membrane to remove impurities, concentrating by using a counter ion permeable membrane, transferring the concentrated liquid into an alcohol precipitation tank, wherein the specific gravity of the concentrated liquid is 1.1, and adding 15kg of absolute ethyl alcohol into the alcohol precipitation tank at the speed of 400rpm of a stirring paddle. Stopping stirring after the ethanol is added, precipitating with ethanol for 24h, collecting supernatant, and concentrating under reduced pressure to obtain ramulus Mori extract. Sample content: the content of alkaloid is 63%, the content of polysaccharide is 23%, the content of flavone is 1%, and the content of amino acid is 5%; DNJ, FAG and DAB are contained in the alkaloid, wherein the content of DNJ is 39%.
Test example Effect of extract on intestinal flora
Female KKAy mice, 8 weeks old, were selected and fed a high calorie diet (Research diet 12451). When the weight of the mice became 40 g or more, multi-index prediction was performed, and with reference to fasting plasma glucose, percent reduction in blood glucose in the ITT test at 40 minutes, blood lipid TG, TC, and body weight, the mice were randomly divided intoA control group to whichA high-fat diet was administered, and an SZ-A treated group to whichA high-fat diet and 200mg/kg of mulberry twig extract (preparation example 5) were administered, with n = 10/group. The administration is performed by gavage 2 times a day.
After 4 weeks of dosing, samples of KKAy mouse feces were collected and analyzed for fecal flora diversity using an interactive environmental microbiota diversity cloud analysis. The results of detecting the microbial diversity in the excrement show that: compared with the control, the composition structure of the intestinal bacterial community of the mice in the SZ-A treatment group is changed (figure 1), which shows that the SZ-A hasA regulating effect on the composition of the intestinal microbial community of the mice; specifically, as shown in fig. 2, at the family level, SZ-A can decrease the abundance of Lactobacillaceae, ruminococcus, rikennellaceae, aerococcus, desulphatovibrio, desulfovibrioceae, Corynebacteriaceae, Enterococcaceae, and christenselliaceae, increase the abundance of Bacteroidaceae, veillonellaceae, Verrucomicrobiaceae, Lachnospiraceae, etc.; at the genus level, SA-A decreased the abundance of Lactobacillus, Allipipes, Aerococcus, Desulfovibrio, Corynebacterium, Enterococcus, Bacteroides, Allobacillus, Faecalibacilum, Lachnocristidium species (FIGS. 2A and 2B).
The present invention has been described above in connection with preferred embodiments, but these embodiments are merely exemplary and merely illustrative. On the basis of the above, the invention can be subjected to various substitutions and modifications, and the substitutions and the modifications are all within the protection scope of the invention.
Claims (9)
1. The application of the mulberry extract in preparing the medicine for regulating the intestinal flora of animals is characterized in that the mulberry extract is prepared according to the following steps:
step 1), preparing a crude extract;
step 2), separation on a cationic resin and/or an optional anionic resin;
step 3), carrying out alcohol precipitation treatment on the resin effluent liquid in the step 2);
optional step 4), concentrating and drying.
2. Use according to claim 1, characterized in that said mulberry extract comprises alkaloids, polysaccharides, flavones and amino acids, preferably said alkaloids comprise DNJ and FAG.
3. Use according to claim 1, characterized in that the modulation of the intestinal flora comprises modulating the flora composition of the intestinal flora, preferably the modulation of the intestinal flora comprises decreasing the abundance of Lactobacillaceae, Ruminococcus, Rikennellaceae, Aerococcus, DesulfoVibrionaceae, Corynebacteriaceae, Enterococcaceae and Christensenellaceae,
increasing the abundance of Bacteroidaceae, Erysipelotrichaceae, Verrucomicrobiaceae, Lachnospiraceae,
wherein, preferably, the Lactobacillaceae comprises Lactobacillus, the Ractococcus comprises Allsipes Alistipes, the Aerococcus comprises Aerococcus, the Desulfornia comprises Desulfovibrio, the Corynebacteriaceae comprises Corynebacterium, the Enterococcus may comprise Enterococcus, the Bacteroides comprises Bacteroides, the Velcrococcaceae comprises Allobacillus and Faecalibacillus, the Lachnospiraceae comprises Lachnococusidium.
4. The use according to claim 1, wherein the animal is a mammal, including humans and rodents.
5. Use according to claim 4, characterized in that the animal glycolipid metabolism is abnormal.
6. The use of claim 4, wherein the animal is a human or a mouse.
7. The use according to claim 1, wherein the medicament further comprises a pharmaceutically acceptable carrier.
8. The use according to claim 1, wherein the medicament further comprises a therapeutically effective amount of at least one therapeutic agent or composition selected from the group consisting of: bifidobacteria, lactobacillin and enteritis tablet.
9. Use according to claim 1, wherein the medicament is administered orally, preferably in a form selected from the group consisting of capsules, tablets, oral solutions, oral emulsions, pills, granules, syrups and powders.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113143996A (en) * | 2021-03-12 | 2021-07-23 | 北京五和博澳药业股份有限公司 | Application of mulberry extract in preparation of composition for treating intestinal inflammation of animals |
| CN113995809A (en) * | 2021-12-08 | 2022-02-01 | 西安交通大学 | Medicine for improving intestinal micro-ecological disorder of children |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110393738A (en) * | 2019-08-27 | 2019-11-01 | 北京五和博澳药业有限公司 | A kind of plant extraction process |
-
2020
- 2020-06-03 CN CN202010492850.3A patent/CN111568949A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110393738A (en) * | 2019-08-27 | 2019-11-01 | 北京五和博澳药业有限公司 | A kind of plant extraction process |
Non-Patent Citations (1)
| Title |
|---|
| 刘率男等: "创新降糖中药桑枝总生物碱调节肠-胰岛轴作用及机制初探", 《中国药理学与毒理学杂志》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113143996A (en) * | 2021-03-12 | 2021-07-23 | 北京五和博澳药业股份有限公司 | Application of mulberry extract in preparation of composition for treating intestinal inflammation of animals |
| CN113143996B (en) * | 2021-03-12 | 2022-10-04 | 北京五和博澳药业股份有限公司 | Application of mulberry extract in preparation of composition for treating intestinal inflammation of animals |
| CN113995809A (en) * | 2021-12-08 | 2022-02-01 | 西安交通大学 | Medicine for improving intestinal micro-ecological disorder of children |
| CN113995809B (en) * | 2021-12-08 | 2022-09-06 | 西安交通大学 | Medicine for improving intestinal micro-ecological disorder of children |
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Address after: No.16 Jincheng Road, Qingyuan Town, Yizhou District, Hechi City, Guangxi Zhuang Autonomous Region 546300 Applicant after: Guangxi Wuhe Boao Pharmaceutical Co.,Ltd. Applicant after: Beijing wuhebao Pharmaceutical Co.,Ltd. Address before: No.16 Jincheng Road, Qingyuan Town, Yizhou District, Hechi City, Guangxi Zhuang Autonomous Region 546300 Applicant before: Guangxi Wuhe Boao Pharmaceutical Co.,Ltd. Applicant before: BEIJING WEHAND-BIO PHARMACEUTICAL Co.,Ltd. |
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