[go: up one dir, main page]

WO2019124803A1 - Composition comprenant un extrait de selaginella rossii warb. ou des fractions de celui-ci pour la prévention ou le traitement de syndromes métaboliques - Google Patents

Composition comprenant un extrait de selaginella rossii warb. ou des fractions de celui-ci pour la prévention ou le traitement de syndromes métaboliques Download PDF

Info

Publication number
WO2019124803A1
WO2019124803A1 PCT/KR2018/014960 KR2018014960W WO2019124803A1 WO 2019124803 A1 WO2019124803 A1 WO 2019124803A1 KR 2018014960 W KR2018014960 W KR 2018014960W WO 2019124803 A1 WO2019124803 A1 WO 2019124803A1
Authority
WO
WIPO (PCT)
Prior art keywords
extract
selaginella
rossii
fraction
ethyl acetate
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/KR2018/014960
Other languages
English (en)
Korean (ko)
Inventor
정태숙
박호용
이화
피아오런쯔
이상우
최상호
리후린
김은진
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Korea Research Institute of Bioscience and Biotechnology KRIBB
Original Assignee
Korea Research Institute of Bioscience and Biotechnology KRIBB
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Korea Research Institute of Bioscience and Biotechnology KRIBB filed Critical Korea Research Institute of Bioscience and Biotechnology KRIBB
Priority to CN201880081289.0A priority Critical patent/CN111491645B/zh
Publication of WO2019124803A1 publication Critical patent/WO2019124803A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • 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
    • A61K36/11—Pteridophyta or Filicophyta (ferns)
    • 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
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • 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
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/328—Foods, ingredients or supplements having a functional effect on health having effect on glycaemic control and diabetes
    • 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
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/332—Promoters of weight control and weight loss

Definitions

  • the present invention relates to a composition for preventing, ameliorating or treating metabolic syndrome containing Selaginella rossii Warb. Extract, fraction thereof, or all of them as an active ingredient.
  • GLP-1 Glucagon-like peptide-1
  • GLP-1 an incretin secreted in human intestinal L cells
  • GLP-1 has receptors in many tissues of the human body.
  • GLP-1 is known to have a strong effect on insulin action in postprandial blood glucose control in response to nutrients ingested into the small intestine (Diabetes Care, 19: 580-586, 1996).
  • pancreatic tissue promotes insulin secretion and cell growth of beta (beta) cells, and suppresses the secretion of glucagon from alpha cells and regulates the body's blood sugar.
  • GLP-1 is associated with lowering of blood glucose, maintaining the sensitivity of pancreatic beta cells, and reduction of appetite
  • GLP-1 receptor agonist is the only weight loss effect of diabetic drugs developed so far (Diabetologia 55: 1577-1596, 2012).
  • Dipeptidyl peptidase-4 (DPP-4; EC 3.4.14.5) belongs to a functionally serine protease (Barrett AJ et al., Arch. Biochem. Biophys., 318: 247-250, 1995) DPP-4 degrades GLP-1 in the small intestine to convert the active GLP-1 into an inactive GLP-1 (9-36) (Eur. J. Biochem., 214: 829-835, 1993). Thus, DPP-4 inhibitors have been used as highly potent agents for the treatment of type 2 diabetes and impaired glucose tolerance.
  • Type 1 diabetes insulin-dependent diabetes
  • arthritis obesity or osteoporosis
  • DPP-IV drugs having an inhibitory action on DPP- It can play a very important role as a candidate drug for treatment.
  • LDL low-density lipoprotein
  • GLP-1 glycopeptide-1
  • DDP-4 lipid-lowering lipoprotein
  • Metabolic syndrome refers to a condition in which the risk factors of death such as diabetes, obesity, insulin resistance, fatty liver, hyperlipidemia, arteriosclerosis, or complications thereof coexist.
  • the incidence of these metabolic syndromes is increasing rapidly in Korea, and it is known that the incidence of metabolic syndrome has increased to the level of advanced countries such as the United States and Western Europe or more.
  • T-CHL low-density lipoprotein cholesterol
  • LDL-C low-density lipoprotein cholesterol
  • Metabolic syndrome has not been developed yet, and it is attempting to treat metabolic syndrome using drugs for the treatment of diabetes, hyperlipidemia and hypertension.
  • Metformin, TZD (thiazolidinediones) drugs, glucosidase inhibitors and dipeptidyl peptidase (DDP) -IV inhibitors which are currently used as diabetic drugs, are expected to be used as medicines for the treatment of metabolic syndrome.
  • blood pressure treatment and hyperlipemia treatment are attracting attention.
  • the factors associated with the cause and treatment of metabolic syndrome include exercise, dietary habits, weight, blood glucose, triglyceride, cholesterol, insulin resistance, adiponectin, leptin, AMP-activated protein kinase (AMPK) , Sex hormones such as estrogen, genetic factors, and in vivo concentrations of malonyl-CoA.
  • AMPK AMP-activated protein kinase
  • Selaginella rossii Warb Is a plant of the order Selaginellaceae and is referred to as a guerrilla or a pit.
  • Selaginella Rossi is a morphologically characterized stem with irregular branching, irregular branching, no stalks attached to the sporangium, and sawtooth on the lower side of the leaf. It has different morphological characteristics I have. No studies have been reported on the efficacy and functionality of the Selaginella radish extract, its fractions, or both.
  • the present inventors have confirmed the prevention, improvement and therapeutic effect of the metabolic syndrome using Selaginella rossii extract, fractions thereof, or all of them, in order to solve the problems of the above prior arts.
  • the Selaginella rossii extract, its fractions, or all thereof significantly inhibited DPP-4 activity, induced an increase in the secretion of insulin in pancreatic beta cells, and secreted GLP-1 in secretory L cells
  • the inventors have confirmed that the expression of the related genes is controlled to promote the secretion of GLP-1, the lipid accumulation is inhibited in 3T3-L1 adipocytes, and the oxidation of LDL is effectively inhibited.
  • Another object of the present invention is to provide a food composition for preventing or ameliorating a metabolic syndrome containing Selaginella rossii extract, a fraction thereof, or all of them as an active ingredient.
  • Another object of the present invention is to provide an antioxidative composition containing Selaginella rossii extract, a fraction thereof, or all of them as an active ingredient.
  • An aspect of the present invention provides a pharmaceutical composition for preventing or treating a metabolic syndrome comprising Selaginella rossii extract, a fraction thereof, or both of them as an active ingredient.
  • the metabolic syndrome may be selected from diabetes, obesity, fatty liver, hyperlipidemia, atherosclerosis, and complications thereof.
  • the Selaginella rossii extract may be water, a lower C 1 -C 4 alcohol, ethyl acetate or a mixed solvent thereof.
  • the Selaginella rossii extract may be any one selected from the group consisting of an ethanol extract, an aqueous ethanol solution, a methanol extract, an aqueous methanol solution and an ethyl acetate extract.
  • the fraction may be ethyl acetate or a butanol fraction.
  • Another aspect of the present invention provides a food composition for preventing or ameliorating a metabolic syndrome comprising Selaginella rossii extract, a fraction thereof, or both.
  • the metabolic syndrome may be selected from diabetes, obesity, fatty liver, hyperlipidemia, atherosclerosis, and complications thereof.
  • the Selaginella rossii extract may be water, C 1 -C 4 lower alcohol, ethyl acetate, or a mixed solvent thereof.
  • the Selaginella rossii extract may be any one selected from the group consisting of an ethanol extract, an aqueous ethanol solution, a methanol extract, an aqueous methanol solution and an ethyl acetate extract.
  • the fraction may be ethyl acetate or a butanol fraction.
  • Another aspect of the present invention provides a pharmaceutical composition for antioxidant comprising Selaginella rossii extract, a fraction thereof, or both of them as an active ingredient.
  • the Selaginella rossii extract of the present invention strongly inhibits diphenylpeptidase-4 (DPP-4) activity, induces increased secretion of insulin in pancreatic beta cells, and inhibits GLP- 1, inhibits fat accumulation in adipocytes, effectively inhibits the oxidation of low density lipoprotein (LDL), improves weight gain, hyperglycemia and glucose tolerance by high fat diet, and increases serum triglyceride levels To be used for prevention or treatment of metabolic syndrome as well as being excellent in antioxidative activity and thus can be usefully used as an antioxidant composition.
  • DPP-4 diphenylpeptidase-4
  • FIG. 1 shows the results of confirming an increase in the amount of insulin secretion according to the treatment with Selaginella lucia ethanol extract or ethyl acetate fraction in pancreatic beta cells induced by high glucose (30 mM).
  • FIG. 2 shows the results of confirming an increase in the amount of GLP-1 secreted by treatment of Selaginella lucia ethanol extract or ethyl acetate fraction in visceral L cells.
  • FIG. 3 shows the results of confirming the increase of expression of proglucagon, PCSK1 / 3, GPR119 and PPAR ⁇ / ⁇ , which are genes involved in the synthesis of GLP-1 by treatment of Selaginella lucia ethanol extract or ethyl acetate fraction in visceral L cells.
  • FIG. 4 is a graph showing the effect of PLN2 on the lipolysis process by the metabolic clock genes ARNTL, PER2, NR1D1 and GLP-1, which regulate the secretion of GLP-1 by treatment with Selaginella lucia ethanol extract or ethyl acetate fraction in visceral L cells Of the cells.
  • FIG. 5 shows a microscopic photograph in which fat accumulation was inhibited by treatment of Selaginella radish ethanol extract or ethyl acetate fraction in 3T3-L1 differentiated adipocytes.
  • FIG. 6 shows the result of confirming inhibition of fat accumulation by treatment of Selaginella lucia ethanol extract or ethyl acetate fraction in 3T3-L1 differentiated adipocytes.
  • FIG. 7 is a graph showing the inhibition of weight gain by the administration of Selaginella radicillium ethanol extract or ethyl acetate extract in a mouse model in which a high fat diet is weighted.
  • FIG. 8 is a graph showing blood glucose lowering by administration of Selaginella lucia ethanol extract or ethyl acetate extract in a model in a mouse model in which hyperglycemia was induced by high fat diet.
  • FIG. 9 shows that the glucose tolerance by the glucose administration in the mouse model induced by the high fat diet method is significantly improved in the Selaginella radish ethanol extract group or the ethyl acetate extract group.
  • FIG. 10 shows the result that the blood glucose level curve of the mouse model in which the high fat diet induces glucose tolerance is improved by the administration of Selaginella radish ethanol extract or ethyl acetate extract.
  • FIG. 11 is a graph showing changes in insulin concentration in blood before and after glucose administration in a mouse model in which high glucose tolerance induces glucose tolerance.
  • the present invention provides a pharmaceutical composition for preventing or treating a metabolic syndrome comprising Selaginella rossii extract, fraction thereof, or all of them as an active ingredient.
  • Selaginella rossii can be used without limitation such as stems, leaves, roots, spores and the like. Selaginella rossii is widely distributed throughout Korea, northern China, Russia, and South Korea, so it is easy to secure raw materials at low cost and can be purchased or collected directly.
  • the extraction method such as hot water extraction, immersion extraction, reflux cooling extraction and ultrasonic extraction can be used.
  • the number of times of extraction is preferably 1 to 5 times.
  • the extraction solvent may be a solvent selected from water, an alcohol or a mixture thereof, preferably water, a C 1 to C 4 lower alcohol (e.g., methanol, ethanol, propanol, isopropanol, butanol, etc.), ethyl acetate, But is not limited thereto.
  • the amount of the extraction solvent is 1 to 15 times the weight of Selaginella rossii .
  • Selaginella rossii aqueous solution extract of ethanol it is extracted at room temperature for 24 to 72 hours, preferably for about 48 hours.
  • Selaginella rossii aqueous methanol solution extract it is extracted at room temperature for 24 to 72 hours, preferably about 48 hours.
  • the Selaginella rossii extract according to the present invention may be any one selected from the group consisting of an ethanol extract, an aqueous ethanol solution, a methanol extract, an aqueous methanol solution and an ethyl acetate extract.
  • the present invention also provides a Selaginella rossii fraction obtained by further isolating the Selaginella rossii extract.
  • Fractionation of the Selaginella rossii extract is carried out by a separation method known in the art.
  • the extract of Selaginella rossii is suspended in a low-alcohol such as methanol, ethanol or propanol and then extracted with a solvent such as hexane, chloroform, ethyl acetate, butanol or water to obtain a fraction have.
  • an aqueous solution of an aqueous ethanol solution of Selaginella rossii is suspended in methanol, the hexane fraction layer is separated by adding hexane, the hexane is separated, and the remaining water layer is washed with chloroform, ethyl acetate, Are sequentially added to prepare each fraction.
  • the fraction may preferably be ethyl acetate or a butanol fraction of Selaginella rossii .
  • the metabolic syndrome can be any one selected from diabetes (e.g., type 1, type 2 diabetes), obesity, fatty liver, hyperlipidemia, arteriosclerosis, and complications thereof.
  • diabetes e.g., type 1, type 2 diabetes
  • complications may include, for example, coronary artery disease, angina pectoris, carotid artery disease, stroke, cerebral arterial sclerosis, hypercholesterolemia, cholesterol stone, hypertriglyceridemia, hypertension, cataract, kidney disease and the like.
  • Selaginella rossii extract or its fraction according to the present invention significantly inhibits DPP-4 activity, induces an increase in insulin secretion in pancreatic beta cells, and inhibits GLP-1 synthesis and secretion-related genes 1 is effective in preventing or treating metabolic syndrome by controlling the expression of GLP-1, promoting the secretion of GLP-1, inhibiting lipid accumulation in 3T3-L1 adipocytes and effectively inhibiting LDL oxidation.
  • the pharmaceutical composition of the present invention may contain a pharmaceutically acceptable carrier and may be in the form of powders, granules, tablets, capsules, suspensions, emulsions, oral preparations such as syrups and aerosols, external preparations, Can be formulated in the form of sterile injectable solutions.
  • Such pharmaceutically acceptable carriers may be those conventionally used in the art such as lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, But are not limited to, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
  • the pharmaceutical composition of the present invention includes diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, surfactants, and other pharmaceutically acceptable additives.
  • the pharmaceutical composition of the present invention when formulated into a solid preparation for oral use, it includes tablets, pills, powders, granules, capsules and the like.
  • a solid preparation may contain at least one excipient such as starch, calcium carbonate, Sucrose or lactose, gelatin, and the like, including, but not limited to, lubricants such as magnesium stearate, talc, and the like.
  • the pharmaceutical composition of the present invention when formulated orally for oral use, it includes suspensions, solutions, emulsions, syrups and the like, and includes, but is not limited to, diluents such as water and liquid paraffin, wetting agents, sweeteners, fragrances and preservatives.
  • diluents such as water and liquid paraffin, wetting agents, sweeteners, fragrances and preservatives.
  • the pharmaceutical composition of the present invention when formulated for parenteral use, it may contain a sterilized aqueous solution, a non-aqueous solvent, a suspending agent, an emulsion, a lyophilized preparation and a suppository.
  • a non-aqueous solvent examples include propylene glycol, polyethylene glycol, Vegetable oils such as oils, injectable esters such as ethyl oleate, and the like.
  • suppositories include, but are not limited to, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
  • the dosage of the Selaginella rossii extract or its fraction contained in the pharmaceutical composition of the present invention varies depending on the condition and body weight of the patient, the age, the degree of the disease, the drug form, the administration route and the period, Can be appropriately selected.
  • the Selaginella rossii extract or its fractions may be administered at a dose of 0.0001 to 100 mg / kg, preferably 0.001 to 10 mg / kg per day, Or may be administered in divided doses.
  • the pharmaceutical composition of the present invention may be administered to mammals such as rats, mice, livestock, humans, and the like by various routes, for example, oral, intraperitoneal or intravenous, muscular, subcutaneous, intrauterine, .
  • the present invention also provides a food composition for preventing or ameliorating a metabolic syndrome comprising Selaginella rossii extract, a fraction thereof, or all of them as an active ingredient.
  • the food composition of the present invention can be used as a health functional food.
  • the term "functional food” as used herein means a food produced or processed by using raw materials or ingredients having functionality useful to the human body according to the Act on Health Functional Foods, and “functional” refers to the structure and functions of the human body Means taking nutrients for the purpose of obtaining a beneficial effect for health use such as controlling nutrients or physiological action.
  • the food composition of the present invention may contain conventional food additives, and the suitability of the term "food additives" as referred to above is to be determined by the Food and Drug Administration according to the General Rules and General Test Methods approved by the Food and Drug Administration It shall be judged according to standards and standards for items.
  • Examples of the substances found in the above-mentioned "food additives” include natural compounds such as ketones, chemical compounds such as glycine, potassium citrate, nicotinic acid and cinnamic acid, coloring pigments, licorice extracts, crystalline cellulose, high- L-glutamic acid sodium preparations, noodle-added alkalis, preservative preparations, tar pigment preparations and the like.
  • the food composition of the present invention may contain 0.01 to 95% by weight, preferably 1 to 80% by weight, of the Selaginella rossii extract, its fractions or all of them, based on the total weight of the composition.
  • the Selaginella rossii extract, fractions thereof or all of them contained in the food composition of the present invention can be obtained in the same manner as the extraction method mentioned in the production of the above pharmaceutical composition.
  • the food composition of the present invention can be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, and circles for the purpose of preventing and / or improving the metabolic syndrome.
  • the health functional food in the form of tablets may be prepared by granulating a mixture of Selaginella rossii extract, its fractions or both, excipients, binders, disintegrants, and other additives in a conventional manner , A lubricant, and the like may be put in a compression molding, or the mixture may be directly compression molded.
  • the health functional food of the tablet form may contain a mating agent and the like if necessary, and may be sieved to a suitable skin care agent if necessary.
  • the hard capsule in a capsule form of health functional food may be prepared by mixing a conventional hard capsule with a mixture of Selaginella rossii extract, a fraction thereof, or all of them, and additives such as excipients or the like, And the soft capsule can be prepared by filling a capsule base such as gelatin with a mixture of Selaginella rossii extract, fraction thereof, or all of them, and additives such as excipients.
  • the soft capsule may contain a plasticizer such as glycerin or sorbitol, a coloring agent, a preservative and the like, if necessary.
  • the ring-shaped health functional food can be prepared by molding Selaginella rossii extract, its fractions, or a mixture of all of these, excipients, binders, disintegrants, etc., by an appropriate method, and if necessary, It may also be converted into starch, talc or a suitable substance.
  • the granular health functional food may be prepared by granulating a mixture of Selaginella rossii extract, fractions thereof, all of them, excipients, binders, disintegrants and the like by a suitable method, and if necessary, And the like.
  • the total amount of the 12- 5.0% or less and that passing through the 45-well body may be 15.0% or less of the total amount.
  • Examples of foods to which the extract of the present invention can be added include beverages, gums, vitamin complexes, and drinks, and include all health functional foods in a conventional sense.
  • the present invention also provides an antioxidant composition comprising Selaginella rossii extract, a fraction thereof, or all of them.
  • antioxidant refers to a function to inhibit, reduce or control the generation or reaction of hydroxyl radicals generated from the hydrogen peroxide or hydrogen peroxide generated from the free radicals, the free radicals generated in the body in a narrow range
  • the broad range refers to the action of inhibiting, reducing or controlling the generation of an oxidation reaction occurring in the natural world.
  • the antioxidant is understood as a narrow range of antioxidants and can be understood as an action that inhibits, reduces or controls the production or reaction of free radicals or hydrogen peroxide, which occurs mainly at the cellular level, but is not particularly limited thereto Do not.
  • the Selaginella rossii extract, fractions thereof or all of them according to the present invention can increase the activity of antioxidant enzymes or increase the protein expression of antioxidant enzymes. In particular, it has an excellent effect in terms of effectively suppressing oxidation of LDL.
  • the antioxidant composition can be used in pharmaceutical compositions, food compositions, cosmetic compositions, and the like.
  • the present invention provides a method of treating a metabolic syndrome comprising administering to a subject a Selaginella rossii extract, a fraction thereof, or both.
  • Selaginella rossii extract, fraction thereof or all of them ","metabolic syndrome ",and” administration "and the like are the same as described above in the present invention.
  • the subject refers to an animal and can typically be a mammal capable of exhibiting beneficial effects with the Selaginella rossii extract of the present invention, fractions thereof, or both.
  • a preferred example of such a subject may include primates such as humans.
  • Such subjects may also include all subjects with or at risk of having symptoms of the metabolic syndrome.
  • the present invention also provides the use of said Selaginella rossii extract, fractions thereof, or both, in the manufacture of a medicament for the treatment of metabolic syndrome.
  • the present invention also provides a composition comprising said Selaginella rossii extract, fractions thereof, or both, for use in the treatment of metabolic syndrome.
  • the present invention also provides said Selaginella rossii extract, fractions thereof, or all of these for the treatment of metabolic syndrome.
  • Selaginella rossii Warb. (Origin: China, Yanbian) and dried at room temperature.
  • the dried material was cut to a suitable size and pulverized using a blender mixer to obtain a pulverized material.
  • the 95% ethanol extract of Selaginella rosin in Example 1 was suspended in 10% methanol, and the same amount of n-hexane was added thereto. After shaking, the mixture was allowed to stand to separate into an upper layer composed of hexane and an aqueous layer below The fractionation process for separating only the upper layer was repeated three times to prepare hexane fractions.
  • the chloroform fraction, the ethyl acetate fraction, the butanol fraction and the water fraction were successively added to the water layer in the same manner, and chloroform, ethyl acetate and butanol were sequentially added to the aqueous layer in succession after shaking, and the mixture was left to concentrate under reduced pressure to obtain ethyl Acetate fraction and 190 mg of the butanol fraction.
  • the 95% methanol extract, 70%, 95% ethanol extract, ethyl acetate extract and ethyl acetate fraction of Selaginella radix according to the present invention showed very high DPP-4 inhibitory activity.
  • the IC 50 concentrations of the 95% methanol extract, 70%, 95% ethanol extract and ethyl acetate extract were 18.0, 18.2, 18.8 and 7.9 ⁇ g / ml, respectively.
  • the IC 50 concentration of the ethyl acetate fraction was 4.6 ⁇ g / ml High DPP-4 inhibitory activity. From these results, the excellent effect of the Selaginella radish extract and its fractions was confirmed.
  • the mouse pancreatic ⁇ cell line MIN6 cells were cultured in Dulbecco's Modified Eagle's medium (DMEM, Hyclone) containing 15% fetal bovine serum (FBS, Gibco), 100 units / ml penicillin and 100 ⁇ g / ml streptomycin °C incubated in a humid 5% CO 2 incubator.
  • DMEM Dulbecco's Modified Eagle's medium
  • FBS fetal bovine serum
  • Cells were plated at a rate of 1 ⁇ 10 5 per well on a 24-well plate and cultured in a humidified 5% CO 2 incubator at 37 ° C. After 48 hours, the cells were first replaced with DMEM medium containing no glucose and left for 60 minutes. Then, the Selaginella radish extract and fraction samples according to the present invention were added to a DMEM medium containing high glucose (30 mM) And reacted for 30 minutes. Control groups were used without sample addition under the same conditions, and the insulin secreted into the medium was measured using an ELISA insulin kit (Alpco diagnostics).
  • the ethanol extract of Selaginella radix according to the present invention was found to induce 55.8% insulin secretion increase at a concentration of 50 ⁇ g / ml compared to the control. It was also confirmed that treatment of the ethyl acetate fraction (50 ⁇ g / ml) induced 92.7% increase in insulin secretion (approximately 1.7 times of the extract) under the same conditions as the control group. From these results, the excellent effect of the Selaginella radish extract and its fractions was confirmed.
  • NCI-H716 cells a human intestinal L cell line
  • RPMI 1640 medium containing 10 mM hydroxyethyl piperazine ethane sulfonic acid (HEPES, Hyclone), 100 units / ml penicillin and 100 ⁇ g / ml streptomycin G) in a 5% CO 2 incubator at 37 ° C in a humidified atmosphere.
  • HEPES hydroxyethyl piperazine ethane sulfonic acid
  • the extract of Selaginella radish (50 ⁇ g / ml) according to the present invention increased the secretion of GLP-1 in NCI-H716 L cells by 37.9% as compared with the control. It was also confirmed that treatment of the ethyl acetate fraction (50 ⁇ g / ml) induces an excellent GLP-1 secretion increase of 114.4% (about 3 times of the extract) compared with the control group under the same conditions. From these results, the excellent effect of the Selaginella radish extract and its fractions was confirmed.
  • RNA was isolated using a TRI reagent (Ambion) in a cell group treated with a Selaginella radish sample according to the present invention for 24 hours, and then cDNA was synthesized using a High-capacity cDNA Reverse Transcription kit (Applied Biosystems) Respectively.
  • Real-Time PCR system (Applied Biosystems) using SYBR Green Master (Roche) using the characteristics of SYBR Green intercalated into double strand deoxyribonucleic acid (dsDNA) with synthesized oligos to amplify each gene , Foster City, CA).
  • the results were expressed quantitatively by the expression of GAPDH.
  • the primers used were confirmed to form a single amplicon of about 150 to 200 bp in the PCR amplification process, and their nucleotide sequences are shown in Table 2 below.
  • GGCACCACACCTTCTACAAT (SEQ ID NO: 1) GCCTGGATAGCAACGTACAT (SEQ ID NO: 2) ARNTL GAGCGGCTCATAGATGCAAAA (SEQ ID NO: 3) GTCGTGCTCCAGAACATAATCG (SEQ ID NO: 4) GPR119 CCATGGCTGGAGGTTATCGAT (SEQ ID NO: 5) AGACACAGTACGGAGAGCTTTGAA (SEQ ID NO: 6) NR1D1 CGGAGCATCCAGCAGAACAT (SEQ ID NO: 7) GCGATTGATGCGGACGAT (SEQ ID NO: 8) PCSK1 / 3 GAGTGGGTCCTAGAGATTGAAAACA (SEQ ID NO: 9) GCCATAGAGTACGAGGGTGAACTT (SEQ ID NO: 10) PER2 AGCGTTACCTCTGAGCACATTG (SEQ ID NO: 11) CATCGCTGAAGGCATCTCTTT (SEQ ID NO: 12) PLIN2 C
  • GLP-1 production is regulated by interfering with G-protein-coupled receptor 119 (GPR119) and ⁇ -catenin / TCF-4 pathway mediating GLP-1 secretion as a lipid receptor in food and expressing proglucagon
  • GPR119 G-protein-coupled receptor 119
  • ⁇ -catenin / TCF-4 pathway mediating GLP-1 secretion as a lipid receptor in food and expressing proglucagon
  • PPAR ⁇ / ⁇ peroxisome proliferator-activated receptor beta or delta
  • ARNTL aryl hydrocarbon receptor nuclear translocator-like protein
  • PER2 period circadian clock 2
  • N1D1 nuclear receptor subfamily 1 group D member 1
  • 3T3-L1 cells were cultured in DMEM (Hyclone) containing 10% calf serum (Gibco), 2 mM L-glutamin, 100 units / ml penicillin and 100 ⁇ g / ml streptomycin. °C incubated in a humid 5% CO 2 incubator.
  • the extract of Selaginella radish (80 ⁇ g / ml) according to the present invention showed an effect of inhibiting fat accumulation in differentiated adipocytes.
  • ethyl acetate fraction (20, 40 ⁇ g / ml) showed significant fat accumulation inhibitory effect of 44.8% and 100.0% in differentiated adipocytes, respectively.
  • the extract of Selaginella radish according to the present invention and the fraction thereof can exhibit excellent anti-obesity activity.
  • LDL was isolated from human plasma using an ultracentrifuge, and the oxidation of LDL was induced using Cu 2+ , (1994) Methods in Enzymology Vol. 234, Oxygen radicals in biological systems Part D (TBARS) was used to measure dialdehyde, an oxidation product of unsaturated fatty acids (Packer, L. Ed.
  • the present invention exhibited excellent LDL antioxidative activity, and the extracts of 95% ethanol and ethyl acetate showed 69.9% and 73.3% at 20 ⁇ g / ml, respectively, , And the ethyl acetate fraction and the butanol fraction showed excellent LDL oxidation inhibitory activity of 79.5% and 72.0% at the concentration of 10 ⁇ g / ml, respectively. From these results, the excellent effect of the Selaginella radish extract and its fractions was confirmed.
  • Example 8 Prevention of metabolic syndrome in an in vivo animal model of Selajinella extract
  • mice Male C57BL / 6J mice were purchased from Life Mouse Center, Korea Research Institute of Bioscience and Biotechnology. The experimental animals were freely fed with the basic diet (10 kcal% fat, D12450B) and water for 3 weeks, and then they were adapted to the laboratory environment. The experimental groups were classified as follows:
  • the experimental group was tested for 10 weeks to observe antidiabetic and anti-obesity effects on body weight, blood glucose and glucose tolerance.
  • the environment of the animal breeding room was kept constant at constant temperature (22 ⁇ 2 ° C), humidity (50 ⁇ 5%) and light period (lighted 07:00 ⁇ 19:00) at 12 hour intervals and 5 animals , And diets and drinking water were freely ingested. Dietary intake and body weight were measured and recorded at regular intervals every week. Twelve-hour fasting followed by blood sampling was performed using Accu-check active test strips (Roche). The animals were fasted for 12 hours before sacrifice, and capillary tubes were used to collect blood from hepatocytes and heparin was used to prevent the coagulation. For blood biochemical tests, 800 g, Plasma was separated by centrifugation at 4 ° C for 15 minutes and stored at -70 ° C for analysis. The organ tissues (pancreas, liver and adipose tissue) of each experimental animal were immediately removed after blood collection and weighed.
  • results were expressed as means ⁇ standard deviation.
  • the differences between the groups were analyzed by one-way ANOVA followed by Turkey's post hoc test (JMP ® software, SAS Institute Inc., USA) And less than 5% ( P ⁇ 0.05). That is, a, b, c indicated by superscripts indicate statistical significance between the other groups.
  • Example 8-1 the body weight of each experimental animal of Example 8-1 was measured by weight change at intervals of one week.
  • the body weight of the control group consuming the high fat diet was significantly Body weight was increased, whereas the body weight of the test group consumed Selaginella rosini ethanol extract and acetate extract with high fat diet decreased from 3 weeks in the control group and decreased by 4.1% and 12.9% in the 10th week, respectively.
  • liver weight of the control group was 0.83 g
  • liver weight of the control group was 1.24 g
  • hepatic weights of the ethanol extract group and the ethyl acetate extract group were 1.16 g and 0.98 g
  • the increase in liver weight was inhibited by the ingestion of Selaginella radish extract.
  • pancreas weight of the control group was 0.13 g
  • the pancreas weight of the control group was increased to 0.18 g
  • the pancreas weights of the ethanol extract group and the ethyl acetate extract group were 0.16 g and 0.15 g, respectively, Respectively.
  • the weight of the adipose tissue of the test group was determined to be 1.22 g in the negative control group, 5.33 g in the control group , Whereas the weight of fat in the ethanol extract and ethyl acetate extract groups was 5.10 g and 4.62 g, respectively.
  • the fasting blood glucose level of the control group consuming the high fat diet showed a significant increase in blood glucose level compared to the negative control group at the 6th week, whereas the administration of Selaginella radish extract inhibited the increase of blood glucose,
  • the fasted glucose level at 10th week in the acetate extract group was 26.8% lower than that of the control group.
  • the blood glucose level at 60, 90 and 120 minutes of Selaginella radish extract was significantly reduced as compared with the control group.
  • the area under the curve (AUC) of FIG. 10 was also lower than that of the control group.
  • the insulin concentration in the control group was significantly increased compared to the negative control group before the glucose administration and 30 minutes after the glucose administration, whereas the insulin concentration in the ethanol extract group was decreased compared to the negative control group.
  • the insulin concentration in the extract group was significantly decreased. This indicates that the sensitivity of insulin secretion by glucose administration is increased. From the above results, the excellent blood glucose control effect of Selaginella radish extract was confirmed in an in vivo animal experiment.
  • Example 8-1 blood glucose was measured from each animal and blood glucose was measured and the HbA1c, insulin and insulin resistance index (HOMA-IR index) were measured on the separated plasma, Total cholesterol (TC) and triglyceride levels were measured, and AST and ALT, which are indicators of liver function, were measured.
  • HbA1c insulin and insulin resistance index
  • TC Total cholesterol
  • triglyceride levels were measured
  • AST and ALT which are indicators of liver function
  • the glycated hemoglobin was measured using an Eisai's glycosylated hemoglobin cartridge [Infopia], and the insulin concentration was measured using an Insulin ELISA kit (Alpco diagnostics), and the insulin resistance index was calculated according to the reference (Biochem. Biophys. Res. Commun. Insulin concentration (ng / mL) x 24.8 x glucose concentration (mg / dL) divided by the calculation formula according to the following formula (341: 507-514, 2006)
  • the total cholesterol, triglyceride, and AST and ALT levels which are indicators of lipid composition, were determined by using the individual measurement kit purchased from Asan Pharmaceuticals. The results are shown in Table 5 below.
  • the control group showed significantly higher fasting glucose, glycated hemoglobin, insulin, insulin resistance index, total cholesterol, and triglyceride compared to the negative control group, while the ethanol extract of Selaginella los and ethyl acetate
  • the administration of the extract decreased the hyperglycemia induced by high fat diet.
  • glucose concentration glycated hemoglobin of ethanol extract group and ethyl acetate extract group were decreased by 12.0% and 14.7%, respectively, and insulin concentration was decreased by 51.1% in the ethyl acetate extract group compared to the control group.
  • Insulin resistance index was significantly decreased by 21.3% and 67.3% in the ethanol extract and ethyl acetate extract groups, respectively.
  • Serum triglyceride levels were decreased by 16.7% and 17.9% in the ethanol extract and ethyl acetate extract groups, respectively, compared with the control group.
  • AST and ALT concentrations in the liver were lower than 40 IU / L in all groups, but they were slightly increased in the control group compared to the negative control group.
  • AST and ALT in the ethyl acetate extract group were significantly decreased compared to the control group. From the above results, it was confirmed in the in vivo animal experiment that lipid lowering effect and hepatoprotective effect in addition to the blood glucose controlling effect of Selaginella radish extract were confirmed.
  • Selaginella rossii extract prepared in Example 1 or 2 and / or the fraction thereof were uniformly mixed with crystalline cellulose, starch and the like, and then granulated together and mixed with magnesium stearate, sucrose fatty acid ester or the like And pressed to produce tablets.
  • Table 6 shows the constituents used in the tablet and the amount thereof used.
  • Selaginella rossii extract and / or its fractions prepared according to Example 1 or 2 were uniformly mixed with shell calcium, crystalline cellulose and the like, and then filled in gelatin capsules to prepare capsules.
  • Table 7 shows the constituents used in the manufacture of capsules and their amounts used.
  • Selaginella rossii extract prepared according to Example 1 or 2 and / or its fractions, 10% by weight of liquid fructose, 2% by weight of honey, 2% by weight of apple juice concentrate (60bx) 0.5% by weight of guarana extract powder, 0.5% by weight of citric acid, 0.1% by weight of sodium citrate and 0.1% by weight of taurine, and then purified water was added thereto to prepare a liquid preparation.
  • Selaginella rossii extract and / or its fractions prepared according to Example 1 or 2 were uniformly mixed with citric acid, oligosaccharide, moss concentrate, plum concentrate, taurine, etc., and purified water was added thereto for about 1 hour After stirring and heating at 85 ° C, the resulting solution was filtered and sterilized in a sterilized container, sealed sterilized, and stored in a refrigerator to prepare a beverage.
  • Table 8 shows the constituents used in the manufacture of health beverages and their amounts used.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Mycology (AREA)
  • Botany (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Polymers & Plastics (AREA)
  • Child & Adolescent Psychology (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Medical Informatics (AREA)
  • Microbiology (AREA)
  • Epidemiology (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

La présente invention concerne une composition pour prévenir, améliorer ou traiter des syndromes métaboliques comprenant un extrait de Selaginella rossii Warb., des fractions de celui-ci, ou les deux, en tant que principes actifs. La composition de la présente invention inhibe fortement la diphénylpeptidase-4 (DPP-4), induit une sécrétion accrue d'insuline dans les cellules bêta pancréatiques, favorise une sécrétion accrue de GLP-1, inhibe l'accumulation de graisse dans les adipocytes, inhibe efficacement l'oxydation des lipoprotéines de faible densité (LDL), améliore le gain de poids, améliore la tolérance à l'hyperglycémie et au glucose par un régime riche en matières grasses, abaisse les taux de triglycérides dans le sang et assure une protection efficace du foie. Ainsi, la présente invention peut être efficacement utilisée pour prévenir ou traiter des syndromes métaboliques et présente également une excellente activité antioxydante, si bien qu'elle peut être efficacement utilisée en tant que composition antioxydante.
PCT/KR2018/014960 2017-12-18 2018-11-29 Composition comprenant un extrait de selaginella rossii warb. ou des fractions de celui-ci pour la prévention ou le traitement de syndromes métaboliques Ceased WO2019124803A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201880081289.0A CN111491645B (zh) 2017-12-18 2018-11-29 包含鹿角卷柏提取物、其分馏物的用于预防或治疗代谢综合症的组合物

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2017-0174342 2017-12-18
KR20170174342 2017-12-18

Publications (1)

Publication Number Publication Date
WO2019124803A1 true WO2019124803A1 (fr) 2019-06-27

Family

ID=66993608

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2018/014960 Ceased WO2019124803A1 (fr) 2017-12-18 2018-11-29 Composition comprenant un extrait de selaginella rossii warb. ou des fractions de celui-ci pour la prévention ou le traitement de syndromes métaboliques

Country Status (3)

Country Link
KR (1) KR102036302B1 (fr)
CN (1) CN111491645B (fr)
WO (1) WO2019124803A1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102335262B1 (ko) * 2019-09-26 2021-12-07 한국생명공학연구원 셀라지넬라 로씨 추출물을 포함하는 피부 노화 방지 및 피부 주름 개선용 화장료 조성물
CN115304661B (zh) * 2022-05-28 2024-03-15 西南民族大学 一种环肽类化合物和用途
KR102852283B1 (ko) 2023-04-04 2025-08-29 제너럴바이오(주) 구실사리 추출물을 유효성분으로 포함하는 항산화 및 항염증 조성물

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20130081852A (ko) * 2012-01-10 2013-07-18 서웅진 부처손 추출물 또는 이의 분획물을 포함하는 면역력 강화용 조성물
KR20130113626A (ko) * 2012-04-06 2013-10-16 충북대학교 산학협력단 양치식물의 추출물을 유효성분으로 포함하는 당뇨 또는 비만의 예방 또는 치료용 조성물
KR20140002262U (ko) * 2012-10-12 2014-04-22 정덕흥 부처손 티백 제조방법
KR20160116427A (ko) * 2015-03-30 2016-10-10 대구가톨릭대학교산학협력단 부처손으로부터 분리된 화합물을 포함하는 대사성 질환의 예방 또는 치료용 조성물

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101132174B1 (ko) 2010-02-12 2012-04-05 조선대학교산학협력단 에리스리나 아비시니카로부터 얻은 에이엠피케이를 활성화시키는 화합물 및 이를 유효성분으로 포함하는 대사증후군 관련 질환의 예방 또는 치료용 조성물
KR101341200B1 (ko) 2010-06-22 2013-12-12 울산대학교 산학협력단 Ｔｒａｐ８０ 조절제를 유효성분으로 함유하는 대사증후군 치료 또는 예방용 약학조성물

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20130081852A (ko) * 2012-01-10 2013-07-18 서웅진 부처손 추출물 또는 이의 분획물을 포함하는 면역력 강화용 조성물
KR20130113626A (ko) * 2012-04-06 2013-10-16 충북대학교 산학협력단 양치식물의 추출물을 유효성분으로 포함하는 당뇨 또는 비만의 예방 또는 치료용 조성물
KR20140002262U (ko) * 2012-10-12 2014-04-22 정덕흥 부처손 티백 제조방법
KR20160116427A (ko) * 2015-03-30 2016-10-10 대구가톨릭대학교산학협력단 부처손으로부터 분리된 화합물을 포함하는 대사성 질환의 예방 또는 치료용 조성물

Also Published As

Publication number Publication date
KR20190073265A (ko) 2019-06-26
CN111491645B (zh) 2022-09-20
KR102036302B1 (ko) 2019-10-24
CN111491645A (zh) 2020-08-04

Similar Documents

Publication Publication Date Title
WO2012134126A2 (fr) Utilisation de composés isolés à partir de l'écorce de mûrier
WO2021261632A1 (fr) Nouvelle souche de faecalibacterium prausnitzii eb-fpdk11 et utilisation associée
WO2019124803A1 (fr) Composition comprenant un extrait de selaginella rossii warb. ou des fractions de celui-ci pour la prévention ou le traitement de syndromes métaboliques
WO2012008788A2 (fr) Composition contenant de la sérine en tant que principe actif pour la prévention et le traitement de stéatoses hépatiques, et utilisation de celle-ci
WO2022092919A1 (fr) Nouvelle souche de bifidobacterium longum z1 et ses utilisations
WO2014200261A1 (fr) Composition anticancéreuse contenant un extrait médicinal à base de plantes mixte en tant que substance active
WO2021230581A1 (fr) Découverte d'une nouvelle akkermansia muciniphila ak32 et application correspondante pour la prévention ou le traitement d'une lésion intestinale
WO2021261631A1 (fr) Nouvelle souche de picalibacterium prosnich eb-fpdk9 et utilisations associées
KR101994557B1 (ko) 비버눔 스텔라토토멘토섬 추출물, 이의 분획물을 포함하는 대사증후군의 예방 또는 치료용 조성물
WO2016048005A2 (fr) Nouveau dérivé de pipéridine pentadiénoyl et son utilisation
WO2014051359A1 (fr) Composition pharmaceutique comprenant de la néférine comme ingrédient actif de prévention contre un hépatome ou de traitement de ce dernier
WO2014042392A1 (fr) Composition à base de metformine pour la prévention ou le traitement de maladies immunes, notamment le lupus
WO2025048505A1 (fr) Nouvelles bactéries lactiques et leur utilisation
WO2024253467A1 (fr) Nouveau composé pour inhiber la sénescence de cellules souches et son utilisation pharmaceutique
WO2021010791A1 (fr) Composition pour atténuer, prévenir ou traiter des troubles cardiovasculaires, contenant un extrait de salvia miltiorrhiza bioconverti et un extrait de ginseng rouge bioconverti
WO2020251085A1 (fr) Composition pour la prévention ou le traitement du syndrome métabolique, comprenant un extrait de viburnum stellato-tomentosum ou une fraction de ce dernier
WO2019231211A1 (fr) Composition permettant la prévention ou le traitement de maladies allergiques, contenant comme principes actifs des extraits mélangés de deux végétaux ou plus sélectionnés parmi la racine d'asiasarum, la racine de platycodon, et cinnamomi ramulus
WO2013111924A1 (fr) Nouveau composé dérivé d'ishige foliacea et son utilisation
WO2013015611A2 (fr) Composition pour la prévention de dommage de chondrocytes et la régénération de ceux-ci, comprenant un hydrolysat de levure comme principe actif
WO2024038980A1 (fr) Souche de lactobacillus plantarum ku15120 ou son utilisation
WO2015111971A1 (fr) Composition pharmaceutique contenant un ligand gpr119 comme principe actif pour prévenir ou traiter une stéatose hépatique non alcoolique
WO2022060024A1 (fr) Composition contenant un extrait d'agrume en tant que principe actif pour améliorer la santé osseuse
WO2022045668A1 (fr) Composition pour induire un brunissement, contenant des exosomes de lait
WO2019027293A1 (fr) Composition pour la prévention ou le traitement de l'obésité comprenant le ml323 utilisé comme principe actif
WO2014021637A1 (fr) Composition comprenant du rébamipide comme ingrédient actif pour prévenir ou traiter l'hyperlipidémie et des maladies lui sont associées

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 18890531

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 18890531

Country of ref document: EP

Kind code of ref document: A1