WO2018090983A1 - Composé de saponine pour améliorer la microflore intestinale, son procédé de préparation et son utilisation - Google Patents

Composé de saponine pour améliorer la microflore intestinale, son procédé de préparation et son utilisation Download PDF

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WO2018090983A1
WO2018090983A1 PCT/CN2017/111690 CN2017111690W WO2018090983A1 WO 2018090983 A1 WO2018090983 A1 WO 2018090983A1 CN 2017111690 W CN2017111690 W CN 2017111690W WO 2018090983 A1 WO2018090983 A1 WO 2018090983A1
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intestinal flora
group
composition
use according
saponin compound
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PCT/CN2017/111690
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WO2018090983A9 (fr
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刘洁
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北京工商大学
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/42—Cucurbitaceae (Cucumber family)
    • A61K36/424—Gynostemma
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/745—Bifidobacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the invention belongs to the technical field of saponin compounds and preparation and application thereof. Specifically, the present invention relates to a triterpenoid saponin compound extracted and isolated from Gynostemma pentaphyllum, and a preparation method and use thereof.
  • the human intestine is a complex, active, and relatively balanced system that colonizes a large number of complex microbial communities.
  • the human gastrointestinal tract is home to about 10 4 normal bacteria, of which 30-40 dominant bacteria constitute 99% of the total intestinal bacteria.
  • Intestinal microbes contain a wide variety of enzyme systems that can participate in a range of physiological processes such as host energy, material and genetic information transfer. Many studies have shown that there is an inseparable mutual symbiotic relationship between the intestinal flora and the host.
  • the intestinal microbes can form a biological barrier in the intestinal tract, through mass occupying, nutrient competition and various metabolites secreted by them. And bacteriocins play an important role in the digestion, absorption, immune response and metabolic activity of the host.
  • Firmicutes and Bacteroides are two dominant species; at the genus level, Bacteroides, Clostridium, Clostridium, and Bifidobacteria are four types closely related to human health. Related dominant bacteria are also the focus of research on intestinal micro-organisms at this stage. The occurrence and development of chronic diseases such as obesity and hyperlipidemia are closely related to the structural imbalance of intestinal flora.
  • Gynostemma pentahyllum (Thunb.) Makino is a perennial herbaceous genus of the genus Cucurbitaceae, and its main bioactive component is a triterpenoid saponin.
  • composition for preparing an improved intestinal flora (1) a composition for preparing an improved intestinal flora; and/or
  • the composition is a pharmaceutical composition or a food composition.
  • the pharmaceutical composition further comprises a pharmaceutically acceptable carrier.
  • the pharmaceutical composition is an oral agent.
  • the dosage form of the pharmaceutical composition is selected from the group consisting of a tablet, a capsule or a granule.
  • the intestinal flora belongs to the phylum of the genus Bacteroides or the bacillus.
  • the intestinal flora belongs to the sputum microphylaxis or the proteobacteria.
  • the intestinal flora is selected from the group consisting of lactic acid bacteria, bifidobacteria, or Clostridium natto.
  • the intestinal flora is Akkermansia muciniphila.
  • the food composition is a diet food.
  • the pharmaceutically acceptable salt of the total saponin compound is selected from the group consisting of sodium salts, potassium salts, or combinations thereof.
  • the Gynostemma pentaphyllum is a diploid Gynostemma pentaphyllum or a tetraploid Gynostemma pentaphyllum, preferably a tetraploid Gynostemma pentaphyllum.
  • the total saponin compound (designated YJ) comprises one or more compounds selected from the group consisting of:
  • a method for non-therapeutic improvement of intestinal flora in vitro comprising the step of administering a compound according to the first aspect of the invention, or a pharmaceutically acceptable salt thereof, at a locus to be treated.
  • the compound or a pharmaceutically acceptable salt thereof is administered at a concentration of 0.001 to 0.02 ⁇ g/ml, preferably 0.01 to 0.15 ⁇ g/ml, more preferably 0.05. -0.1 ⁇ g/ml.
  • a probiotic composition comprising:
  • a first drug a saponin compound
  • a second drug one or more probiotics selected from the group consisting of lactic acid bacteria, bifidobacteria, Clostridium genus, Akkermansia muciniphila, or a combination thereof;
  • first drug and the second drug are located in the same or different containers.
  • the mass ratio of the first drug to the second drug (in terms of active ingredient) in the probiotic composition is 1:100-100:1, preferably 1: 10-10:1, more preferably 1:5-5:1.
  • the probiotic composition is a pharmaceutical composition or a food composition.
  • a method of improving intestinal flora comprising the step of administering a compound according to the first aspect of the invention, or a pharmaceutically acceptable salt thereof, to a subject in need thereof.
  • the compound or a pharmaceutically acceptable salt thereof is administered at a concentration of 0.001 to 0.02 ⁇ g/ml, preferably 0.01 to 0.15 ⁇ g/ml, more preferably 0.05. -0.1 ⁇ g/ml.
  • Figure 1 shows the preventive effects of different doses of total saponin compound YJ on obesity caused by a high-fat diet.
  • Figure 2 shows the effect of total saponin compound YJ on community diversity of intestinal bacteria at the gate level.
  • A represents low-fat diet feeding
  • B represents high-fat diet feeding
  • C stands for high-fat group + low-dose YJ (100 mg/Kg)
  • D stands for high-fat group + high-dose YJ (300 mg/Kg).
  • Figure 3 shows the effect of total saponin compound YJ on community diversity of gut bacteria at the genus level, A for low fat feed; B for high fat diet; C for high fat + low dose YJ (100 mg/Kg) D represents a high fat group + a high dose YJ (300 mg/Kg).
  • Figure 4 shows the effect of PCOA on total intestinal saponin compound YJ on intestinal flora-genus, A for low-fat diet feeding; B for high-fat diet; C for high-fat group + low-dose YJ (100 mg/kg), D Represents high fat group + high dose YJ (300mg/Kg).
  • Figure 5 shows the effect of total saponin compound YJ on the intestinal flora-gate.
  • HF stands for high fat diet obesity model group
  • HF+YJ stands for high fat diet +300 mg/kg dose YJ.
  • Figure 6 shows the effect of total saponin compound YJ on the diversity of intestinal bacteria in obese mice at the gate level, HF for the high fat diet obesity model group (mouse number HF 1-8); HF+YJ stands for high Fat feed + 300 mg/kg dose YJ (mouse number HF_YJ 1-8).
  • Figure 7 shows the effect of total saponin compound YJ on the microbial diversity of intestinal bacteria in obese mice
  • HF represents the high fat diet obesity model group (mouse number HF 1-8);
  • HF+YJ stands high Fat feed + 300 mg/kg dose YJ (mouse number HF_YJ 1-8).
  • Figure 8 shows the effect of PCA analysis of total saponin compound YJ on intestinal flora diversity in obese mice, HF for high fat diet obesity model group (mouse number HF 1-8); HF+YJ for high fat diet +300 mg/kg dose YJ (mouse number HF_YJ 1-8).
  • the inventors of the present application have extensively and intensively studied the chemical constituents and biological activities of Gynostemma pentaphyllum, and successfully isolated a plurality of new triterpenoid saponins from Gynostemma pentaphyllum, and first discovered the triterpene total saponin compound YJ and One or more monomeric compounds have a function of preventing obesity by improving the intestinal flora of the animal. On the basis of this, the present invention has been completed.
  • the term “about” means that the value can vary by no more than 1% from the recited value.
  • the expression “about 100” includes all values between 99 and 101 and (eg, 99.1, 99.2, 99.3, 99.4, etc.).
  • the terms "containing” or “including” may be open, semi-closed, and closed. In other words, the terms also include “consisting essentially of,” or “consisting of.”
  • Gynostemma pentaphyllum is a dry whole grass of Gynostemma pentaphyllum (Thunb. Makino), which is a perennial climbing herb. Gynostemma pentaphyllum has a long history of eating and was first used in the Ming Dynasty's "Rescue Materia Medica” for wild vegetables. The Japanese folks call it "Gancha Man", a sweet tea substitute or a sweetener for diabetics. Gynostemma pentaphyllum is also one of the plants with ginseng saponin resources outside Wujiake. It has many functions such as nourishing health, anti-cancer, anti-aging, blood fat reduction and blood sugar lowering. It is known as “Southern Ginseng”.
  • Gynostemma pentaphyllum is one of the plants that can be used for health care products announced by the Ministry of Health. Because of its remarkable health care effect and high safety, it is suitable for long-term use. It is often used as a lipid-lowering health tea in the folk.
  • the total saponin compound YJ of the present invention includes, but is not limited to, a saponin compound extracted from Gynostemma pentaphyllum and the like, that is, a series of compounds having a saponin structure.
  • the total saponin compound of the present invention comprises one or more compounds selected from the group consisting of:
  • the composition of intestinal flora is closely related to obesity. Studies at the animal level indicate that compared with normal mice, ob/ob obese mice have increased the number of bacteria in the intestinal flora, and the number of Bacteroides Reduced by 50%; at the human level, 12 fat patients were followed up for treatment with a fat-restricted diet and a carbohydrate-restricted diet. After one year, the weight of the former decreased by 2%, and the weight of the latter decreased by 6%. The 16s rRNA gene study showed that the total amount of energy in the food did not change, and the number of thick-walled bacteria in the intestine after losing weight through two diets. Decreased, while the number of Bacteroides gates increased. The data suggest that an increase in the proportion of Bacteroides/Thick Wall bacteria in the gut contributes to the prevention and treatment of obesity.
  • Akkermansia muciniphila belongs to the family Verrucomicrobiaceae. In May 2013, Belgian researchers published an article on PNAS to discover a "slimming bacteria" by studying a gut bacteria. The liquid medium containing this bacteria can be greatly Change the health of obese mice.
  • the method for preparing a triterpenoid saponin compound of the present invention comprises the following steps:
  • the aerial part of the tetraploid Gynostemma pentaphyllum is extracted with a solvent for 2-5 times, each time 1-3 hours, and the extract is concentrated to obtain an extract;
  • the solvent in the step (1) is selected from the mixture of one or more of methanol, ethanol, acetone or water;
  • the mass ratio of the extract to the water in the step (2) is 1:2-1:15.
  • the ratio of the amount of petroleum ether added to the dispersion in the step (2) is 1:2-5:1;
  • the ratio of the amount of ethyl acetate added to the dispersion in the step (2) is 1:2-5:1;
  • the volume ratio of n-butanol to the dispersion in the step (2) is 1:2 to 5:1.
  • the ethanol-water solution is subjected to a gradient elution at a volume ratio of 20:1 to 100:1; and then separated by Sephadex LH-20 column chromatography, and eluted sequentially with a pure methanol solvent. Collecting fractions containing the compound; one fraction is separated and purified by semi-preparative reversed-phase high performance liquid chromatography in a solvent system of 30% acetonitrile-15% methanol-55% water (vol) to obtain saponin compound 1 in sequence -9.
  • the total saponin compounds of the present invention By investigating the effects of the total saponin compounds of the present invention on the proportion of the intestinal flora of the genus Bacteroides and the thick-walled bacteria, especially the slimming bacteria (Akkermansia muciniphila) in the genus Microsporaceae can be significantly improved, and the mechanism of action thereof is studied. It was found that the compounds of the present invention and their optical isomers, pharmaceutically acceptable salts and solvates can be significantly adjusted high. The intestinal flora caused by the fat diet to prevent obesity.
  • the compounds of the present invention can also be used as food adjuvants or food additives, added to foods for improving the intestinal flora of animals and promoting the colonization of beneficial microorganisms.
  • the invention also provides a pharmaceutical composition
  • a pharmaceutical composition comprising an active ingredient in a safe and effective amount, together with a pharmaceutically acceptable carrier.
  • the "active ingredient” as used in the present invention means the Gynostemma total saponin compound of the present invention.
  • the "active ingredients" and pharmaceutical compositions of the present invention are useful for improving intestinal flora composition and promoting beneficial microbial colonization.
  • it is used to prepare a medicament which improves the intestinal flora of an animal.
  • the pharmaceutical compositions contain from 1 to 2000 mg of active ingredient per dose, more preferably from 10 to 200 mg of active ingredient per dose.
  • the "one dose” is a tablet.
  • “Pharmaceutically acceptable carrier” means: one or more compatible solid or liquid fillers or gel materials which are suitable for human use and which must be of sufficient purity and of sufficiently low toxicity.
  • “compatibility” it is meant herein that the components of the composition are capable of intermingling with the active ingredients of the present invention and with respect to each other without significantly reducing the efficacy of the active ingredients.
  • the carrier includes one or more of a diluent, a filler, a disintegrant, a lubricant, a colorant, a flavoring agent, or other conventional additives.
  • Examples of pharmaceutically acceptable carriers are cellulose and its derivatives (such as sodium carboxymethylcellulose, sodium ethylcellulose, cellulose acetate, etc.), gelatin, talc, solid lubricants (such as stearic acid). , magnesium stearate), calcium sulfate, vegetable oil (such as soybean oil, sesame oil, peanut oil, olive oil, etc.), polyol (such as propylene glycol, glycerin, mannitol, sorbitol, etc.), emulsifier (such as ), a wetting agent (such as sodium lauryl sulfate), a coloring agent, a flavoring agent, a stabilizer, an antioxidant, a preservative, a pyrogen-free water, and the like.
  • cellulose and its derivatives such as sodium carboxymethylcellulose, sodium ethylcellulose, cellulose acetate, etc.
  • gelatin such as sodium carboxymethylcellulose, sodium ethylcellulose, cellulose acetate,
  • the mode of administration of the active ingredient or pharmaceutical composition of the present invention includes oral administration and the like.
  • Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules.
  • the active ingredient is mixed with at least one conventional inert excipient (or carrier), such as sodium citrate or dicalcium phosphate, or mixed with: (a) a filler or compatibilizer, for example, Starch, lactose, sucrose, glucose, mannitol and silicic acid; (b) binders, for example, hydroxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and gum arabic; (c) humectants, For example, glycerin; (d) a disintegrant such as agar, calcium carbonate, potato starch or tapioca starch, alginic acid, certain complex silicates, and sodium carbonate; (e) a slow solvent such as paraffin; (f) Absorbing accelerators, for example, quaternary amine compounds; (g) wetting agents, such as cetyl alcohol and glyceryl monostearate; (h) adsorbents, for example,
  • the solid dosage forms can also be prepared with coatings and shell materials, such as casings and other materials known in the art. They can An opacifying agent is included and the release of the active ingredient in such a composition can be released in a portion of the digestive tract in a delayed manner.
  • coatings and shell materials such as casings and other materials known in the art.
  • An opacifying agent is included and the release of the active ingredient in such a composition can be released in a portion of the digestive tract in a delayed manner.
  • embedding components that can be employed are polymeric and waxy materials.
  • Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups or elixirs.
  • the liquid dosage form may contain inert diluents conventionally employed in the art, such as water or other solvents, solubilizers and emulsifiers, for example, ethanol, isopropanol, ethyl carbonate, ethyl acetate, propylene glycol, 1 , 3-butanediol, dimethylformamide and oils, especially cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil or a mixture of these substances.
  • the compositions may contain adjuvants such as wetting agents, emulsifying and suspending agents, sweetening agents, flavoring agents and perfumes.
  • the suspension may contain suspending agents, for example, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum methoxide and agar or mixtures of these and the like.
  • suspending agents for example, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum methoxide and agar or mixtures of these and the like.
  • compositions for parenteral injection may comprise a physiologically acceptable sterile aqueous or nonaqueous solution, dispersion, suspension or emulsion, and a sterile powder for reconstitution into a sterile injectable solution or dispersion.
  • Suitable aqueous and nonaqueous vehicles, diluents, solvents or vehicles include water, ethanol, polyols, and suitable mixtures thereof.
  • the compounds of the invention may be administered alone or in combination with other therapeutic agents.
  • a safe and effective amount of a compound of the invention is administered to a mammal (e.g., a human) in need of treatment wherein the dosage is a pharmaceutically effective effective dosage, for a 60 kg body weight
  • the dose to be administered is usually from 1 to 2000 mg, preferably from 20 to 500 mg.
  • specific doses should also consider factors such as the route of administration, the health of the patient, etc., which are within the skill of the skilled physician.
  • the present invention obtains a novel triterpenoid saponin compound by extracting and separating from tetraploid Gynostemma pentaphyllum, and the compound and their optical isomers, pharmaceutically acceptable salts and solvates thereof have been used for improving intestinal flora of animals.
  • a novel triterpenoid saponin compound by extracting and separating from tetraploid Gynostemma pentaphyllum, and the compound and their optical isomers, pharmaceutically acceptable salts and solvates thereof have been used for improving intestinal flora of animals.
  • beneficial microbial colonization and to prevent and treat obesity which may be administered in its own form or in combination with a pharmaceutically acceptable carrier;
  • the present invention provides a simple and easy preparation method, which can be completed in a general-purpose device
  • the prepared compound has high purity, good economic benefit and application prospect.
  • the 18kg tetraploid Gynostemma pentaphyllum leaves were weighed by a pulverizer and then extracted by 20L 95% ethanol reflux method (feed ratio: 1:2.6), extracted 3 times for 3h, 2h, 1h, and removed by rotary evaporation. Ethanol to obtain crude extract of Gynostemma pentaphyllum paste.
  • the above extract was dispersed in water, and successively extracted with an equal volume of petroleum ether, ethyl acetate and n-butanol to obtain petroleum ether, ethyl acetate, n-butanol and water extracting sites, respectively.
  • mice After 32 mice were acclimated for one week, they were divided into 4 groups, 8 in each group, and fed in a single cage.
  • group A low-fat group, 10% energy derived from fat
  • group B high-fat group, 45% energy derived from fat
  • group C high-fat group +100 mg/Kg/d YJ
  • group D High fat group +300mg/Kg/d YJ
  • the breeding environment temperature is 22 ⁇ 2°C, the humidity is 30-70%, the mice are free to eat and drink water; the experiment lasts for 12 weeks, the weight is recorded every day, and the food and sterile water are renewed every Tuesday and Friday. Record the amount and record the amount of food consumed. Change the mouse padding weekly and change the cage every month. After 12 weeks, 3 days of fecal volume was collected continuously. Four mice were randomly selected from each group, DNA was extracted, and Illumina Miseq PE250/PE300 was sequenced to analyze the bacterial diversity of the fecal samples.
  • mice were fed with high-fat diet for 4 months and weighed about 40 g. After obesity-resistant mice were removed, they were randomly divided into 2 groups, 8 in each group, and fed in single cages.
  • the model group (HFD) continued to feed high-fat diet.
  • the tube was given a total dose of 300 mg/Kg/d total saponin compound for 2 months, and the body weight was recorded every day. New food and sterile water will be renewed on Tuesdays and Fridays, and a weighing record will be made to record the food intake. Change the mouse padding weekly and change the cage every month. After 2 months, all mice were continuously collected for 3 days of fecal volume, and DNA was extracted for Illumina Miseq PE250/PE300. Sequencing, analysis of the diversity of fecal sample flora.
  • YJ has a great influence on the diversity of the following strains: Bacteroides, Akkermansia muciniphila, lactic acid bacteria and the like.
  • YJ intervention mouse Verrucomicrobiaceae (blue mark) was significantly induced to express, further at the genus level, further proved the total saponin compound weight loss And its induction to Akkermansia muciniphila. Therefore, YJ is a prebiotic substance that specifically promotes the proliferation of Akkermansia muciniphila. Administration of 300 mg/kg YJ significantly increased the content of Akkermansia muciniphila compared to the control group.
  • Figure 7 shows the effect of YJ on the diversity of intestinal bacteria in obese mice at the genus level. Similarly, Akkermansia muciniphila was significantly improved. By PCA analysis, the two groups could be completely separated, demonstrating that YJ is regulating obese mice.
  • the composition of the intestinal flora constitutes a significant effect on the prevention and treatment of obesity (Fig. 8).
  • the above components are uniformly mixed and directly compressed, that is, a tablet composition is obtained, one tablet per oral administration, 2-3 times a day.
  • the above component mixture was uniformly filled into 1000 capsules, one tablet per oral administration, 2-3 times a day.

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Abstract

L'invention concerne un composé de saponine pour améliorer la microflore intestinale, et un procédé de préparation et l'utilisation de celui-ci, le composé de saponine étant un gypénoside. La composition peut améliorer la microflore intestinale et favoriser la colonisation par des micro-organismes caractéristiques.
PCT/CN2017/111690 2016-11-17 2017-11-17 Composé de saponine pour améliorer la microflore intestinale, son procédé de préparation et son utilisation WO2018090983A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201611018050.8A CN107753547B (zh) 2016-11-17 2016-11-17 改善肠道菌群的皂苷类化合物、制备方法及其应用
CN201611018050.8 2016-11-17

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WO2018090983A1 true WO2018090983A1 (fr) 2018-05-24
WO2018090983A9 WO2018090983A9 (fr) 2018-08-09

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Cited By (3)

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Publication number Priority date Publication date Assignee Title
WO2020080641A1 (fr) * 2018-10-17 2020-04-23 서울대학교산학협력단 Composition pour la prévention et le traitement de maladies liées à l'ampk, comprenant un extrait de gynostemma longipes vk1 ou un composé isolé à partir de celui-ci en tant qu'ingrédient actif
CN114984024A (zh) * 2020-11-16 2022-09-02 湖南华宝通制药有限公司 绞股蓝总苷颗粒中具有抑制pcsk9作用的皂苷类化合物的应用
CN116898883A (zh) * 2023-08-18 2023-10-20 善恩康生物科技（苏州）有限公司 Akkermansia muciniphila在制备预防、治疗和/或辅助治疗疼痛的产品中的应用

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108774282B (zh) * 2018-07-23 2021-01-08 中国科学院兰州化学物理研究所 一种绞股蓝中具有抗阿尔茨海默病的达玛烷型三萜皂苷
CN109954018A (zh) * 2019-04-19 2019-07-02 华南理工大学 一种绞股蓝皂苷、含有绞股蓝皂苷的健脑助眠口服液及其制备
CN114642676B (zh) * 2020-12-18 2024-02-13 中国科学院上海营养与健康研究所 人参皂苷在改善肠道菌群结构和/或肠屏障功能的应用
CN114847475B (zh) * 2022-07-05 2022-11-29 广东金骏康生物技术有限公司 一种促进akk菌生长的发酵槐米粉的应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101317627A (zh) * 2008-06-16 2008-12-10 何德永 蛋鸡用乳酸菌饲料
CN104382047A (zh) * 2014-12-03 2015-03-04 青岛根源生物技术集团有限公司 一种绞股蓝益生菌咀嚼片及其制备方法
CN105146538A (zh) * 2015-09-09 2015-12-16 安徽管仲宫神生物科技有限公司 酵素粉的制备方法
CN105146517A (zh) * 2015-09-09 2015-12-16 安徽管仲宫神生物科技有限公司 降低胆固醇的酵素原液及其制备方法

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7112573B2 (en) * 2002-04-19 2006-09-26 Iowa Research, The University Foundation Isoflavone and triterpene glycosides from soybeans
US7544668B2 (en) * 2006-11-17 2009-06-09 Hong Kong Baptist University Saponins derived from Ilex pubescens and method of purifying the same
CN102743420A (zh) * 2012-06-06 2012-10-24 上海交通大学 改善肠道菌群结构的方法及应用
CN104926911B (zh) * 2015-06-04 2017-10-17 上海交通大学 防治肥胖症的三萜皂苷类化合物、制备方法及其应用

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101317627A (zh) * 2008-06-16 2008-12-10 何德永 蛋鸡用乳酸菌饲料
CN104382047A (zh) * 2014-12-03 2015-03-04 青岛根源生物技术集团有限公司 一种绞股蓝益生菌咀嚼片及其制备方法
CN105146538A (zh) * 2015-09-09 2015-12-16 安徽管仲宫神生物科技有限公司 酵素粉的制备方法
CN105146517A (zh) * 2015-09-09 2015-12-16 安徽管仲宫神生物科技有限公司 降低胆固醇的酵素原液及其制备方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
LIU GUOJUAN ET AL.: "Quality Control Study of Capsules of Gynostemma pentaphyllum and Bifidobacterium", CHINESE JOURNAL OF MODERN APPLIED PHARMACY, vol. 18, no. 7, 30 September 2001 (2001-09-30), pages 73 - 75, ISSN: 1007-7693 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020080641A1 (fr) * 2018-10-17 2020-04-23 서울대학교산학협력단 Composition pour la prévention et le traitement de maladies liées à l'ampk, comprenant un extrait de gynostemma longipes vk1 ou un composé isolé à partir de celui-ci en tant qu'ingrédient actif
CN114984024A (zh) * 2020-11-16 2022-09-02 湖南华宝通制药有限公司 绞股蓝总苷颗粒中具有抑制pcsk9作用的皂苷类化合物的应用
CN114984024B (zh) * 2020-11-16 2023-11-21 湖南华宝通制药有限公司 绞股蓝总苷颗粒中具有抑制pcsk9作用的皂苷类化合物的应用
CN116898883A (zh) * 2023-08-18 2023-10-20 善恩康生物科技（苏州）有限公司 Akkermansia muciniphila在制备预防、治疗和/或辅助治疗疼痛的产品中的应用

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