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WO2021034111A1 - Nouveau dérivé de sesquiterpène et son utilisation - Google Patents

Nouveau dérivé de sesquiterpène et son utilisation Download PDF

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WO2021034111A1
WO2021034111A1 PCT/KR2020/011066 KR2020011066W WO2021034111A1 WO 2021034111 A1 WO2021034111 A1 WO 2021034111A1 KR 2020011066 W KR2020011066 W KR 2020011066W WO 2021034111 A1 WO2021034111 A1 WO 2021034111A1
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Prior art keywords
obesity
present
tetramethyloctahydro
added
compound
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Korean (ko)
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황성관
이홍우
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Mfc Co ltd
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Mfc Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/116—Heterocyclic compounds
    • A23K20/121—Heterocyclic compounds containing oxygen or sulfur as hetero atom
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/163—Sugars; Polysaccharides
    • 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
    • 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
    • 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
    • A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
    • C07D317/32—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D317/34—Oxygen atoms
    • C07D317/40—Vinylene carbonate; Substituted vinylene carbonates
    • 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
    • A23V2200/332—Promoters of weight control and weight loss

Definitions

  • the present invention relates to novel sesquiterpene derivatives and uses thereof, and more particularly to novel sesquiterpene derivatives or optical isomers thereof; Pharmaceutical compositions, food compositions, and feed compositions comprising them; And it relates to the use of the prevention or treatment of obesity or metabolic disease.
  • Obesity is one of the diseases that are difficult to avoid in the modern living environment.
  • These diseases increase the risk of occurrence of each other, and are common diseases related to various metabolic changes in living organisms such as aging, stress, and immune function decline.
  • Korean adults over the age of 20 were obese (35.2% of adult males and 28.3% of female adults).
  • a drug currently used as a treatment for obesity its use is very limited because it is known to inhibit the absorption of vitamin D in the body and side effects such as unbearable urgency, fat stool, intestinal gas bloating, and abdominal bloating. .
  • drugs that inhibit fat absorption in the body are not desirable drugs for Koreans, who have relatively less meat intake than Westerners.
  • sibutramine another drug used as a treatment for obesity, side effects such as headache, dry mouth, loss of appetite, insomnia, constipation, increased heart rate, palpitations, and dizziness appear. It is not a topical drug but is known to act on the cerebral central nerve system and its use is extremely limited.
  • Main ingredients extracted from the woody part of cedar ( Cupressus funebris ) or juniper ( Juniperus chinensis ) include (+)-sedrol, alpha-sedrene, beta-sedrene, alpha-funebrin, beta-funebrin, etc.
  • Cedrol and cedrene derivatives are known, and these are sesquiterpene-like compounds composed of three isoprene units.
  • Cedrol and its derivatives are used in various pharmaceutical applications such as psoriasis, atopy, eczema, seborrheic skin composition, scleroderma, skin immune hypersensitivity treatment (Korean Patent No.
  • Cedrol and its derivatives isolated and purified from the woody part of natural cedar or juniper have low solubility in water (21.88mg/L, reference; Int.J of Nanomedicine, 2017) despite showing pharmacological effects in vitro. , 12, pp4850), so there is little absorption in the body, so there is a pharmaceutical barrier that is too large to be developed for practical pharmaceutical use. That is, there is a disadvantage that this cannot be achieved due to low solubility in water when the dose is increased to reach the medicinal capacity.
  • the present invention provides novel sesquiterpene derivatives or optical isomers thereof.
  • the present invention provides a pharmaceutical composition comprising the novel sesquiterpene derivative or optical isomer thereof as an active ingredient.
  • the present invention provides a pharmaceutical composition for preventing or treating obesity or metabolic diseases comprising the novel sesquiterpene derivative or an optical isomer thereof as an active ingredient.
  • the present invention provides a food composition for preventing or improving obesity or metabolic diseases comprising the novel sesquiterpene derivative or optical isomer thereof as an active ingredient.
  • the present invention provides a feed composition for preventing or improving obesity or metabolic diseases comprising the novel sesquiterpene derivative or an optical isomer thereof as an active ingredient.
  • the present invention provides a method for preventing or treating obesity or metabolic diseases comprising administering the pharmaceutical composition to an individual.
  • the present invention provides the use of the novel sesquiterpene derivative or optical isomer thereof for the prevention or treatment of obesity or metabolic diseases.
  • the present invention provides the use of the novel sesquiterpene derivative or optical isomer thereof for the manufacture of a medicament for the prevention or treatment of obesity or metabolic disease.
  • new sesquiterpene derivatives or optical isomers thereof show high solubility in water, and weight and visceral fat mass
  • triglycerides, blood sugar, insulin concentration and confirmed the excellent effect of reducing the concentration of triglycerides in liver tissue, and completed the present invention.
  • the present invention provides a novel sesquiterpene derivative, that is, a compound represented by the following Chemical Formulas 1 to 12, or an optical isomer thereof.
  • the present invention provides a compound represented by Formula 3, Formula 4, Formula 6 to Formula 8, or an optical isomer thereof.
  • the compounds represented by Chemical Formulas 1 to 12 of the present invention or optical isomers thereof may reduce body weight, visceral fat mass, plasma total cholesterol, triglyceride, blood sugar, and insulin concentration, and triglyceride concentration in liver tissue. Accordingly, the compounds represented by Chemical Formulas 1 to 12 of the present invention or optical isomers thereof may be usefully used in the prevention or treatment of obesity or metabolic diseases.
  • the compounds represented by Chemical Formulas 1 to 12 of the present invention or optical isomers thereof reduce the fat content of the nematode nematode (Figs. 1 and 2), and reduce the weight and visceral fat mass of the mouse.
  • Table 2 it was confirmed that plasma total cholesterol, triglyceride, blood sugar and insulin concentrations and hepatic triglyceride concentrations were reduced in mice (Table 3).
  • composition comprising novel sesquiterpene derivative or optical isomer thereof, use thereof, and treatment method using the same
  • the present invention provides a pharmaceutical composition comprising any one or more of the compounds represented by the following Chemical Formulas 1 to 12 or optical isomers thereof as an active ingredient.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of obesity or metabolic diseases comprising any one or more of a compound represented by the following Chemical Formulas 1 to 12 or optical isomers thereof as an active ingredient.
  • the pharmaceutical composition may include a compound represented by Formula 3, Formula 4, Formula 6 to Formula 8, or any one or more of optical isomers thereof as an active ingredient.
  • the term "obesity" of the present invention refers to a state in which an excessive amount of fat is accumulated in the body, which causes various types of metabolic diseases such as diabetes, hyperlipidemia, fatty liver, arteriosclerosis, and the like.
  • metabolic disease refers to a disease caused by metabolic disorders in vivo, and in the present invention, the metabolic disease may be selected from the group consisting of diabetes, hyperlipidemia, fatty liver, but is limited thereto. no.
  • diabetes refers to a chronic disease characterized by a relative or absolute lack of insulin resulting in glucose-intolerance.
  • the diabetes includes all types of diabetes, for example, type 1 diabetes, type 2 diabetes, and inherited diabetes.
  • Type 1 diabetes is insulin dependent diabetic disease, which is mainly caused by the destruction of beta cells.
  • Type 2 diabetes is insulin nondependent diabetic disease, which is caused by insufficient insulin secretion after a meal or by insulin resistance.
  • a composition comprising as an active ingredient any one or more of the compounds represented by Chemical Formulas 1 to 12 of the present invention or optical isomers thereof, prevents or treats type 1 diabetes, more preferably, type 2 diabetes caused by insulin resistance. It can have an effect.
  • hyperlipidemia refers to a disease caused by a high level of fat in the blood due to inadequate lipid metabolism such as triglycerides and cholesterol. Specifically, it refers to a state in which lipid components such as neutral fat acid, LDL (low density lipid), cholesterol, phospholipids, and fatty acids in the blood are increased, and the frequency of occurrence thereof is increased. It may refer to, but is not limited to, hyper-cholesterol disease.
  • fatty liver refers to a condition in which an excessive amount of fat is accumulated in hepatocytes due to liver metabolism disorder, which is various such as angina pectoris, myocardial infarction, stroke, arteriosclerosis, and pancreatic composition. It causes disease.
  • a composition comprising as an active ingredient any one or more of the compounds represented by Chemical Formulas 1 to 12 or optical isomers thereof of the present invention is weight, visceral fat mass, plasma total cholesterol, triglyceride, blood sugar, and insulin concentration, and liver tissue neutrality. It can reduce fat concentration. Accordingly, a composition comprising as an active ingredient any one or more of the compounds represented by Chemical Formulas 1 to 12 or optical isomers thereof of the present invention may be usefully used in the prevention or treatment of obesity or metabolic diseases.
  • a composition comprising as an active ingredient any one or more of the compounds represented by Chemical Formulas 1 to 12 or optical isomers thereof of the present invention reduces the fat content of the nematode (Fig. 1 and Figure 2), as well as reducing the body weight and visceral fat mass of the mouse (Table 2), it was confirmed that the plasma total cholesterol, triglyceride, blood glucose and insulin concentrations and liver triglyceride concentration of the mouse were reduced (Table 3).
  • prevention of the present invention means any action that inhibits or delays the onset of a disease by administration of a compound or composition.
  • treatment refers to any action in which symptoms of an individual suspected of and onset of a disease are improved or beneficially altered by administration of a compound or composition.
  • the pharmaceutical composition of the present invention may include one or more pharmaceutically acceptable carriers in addition to any one or more of the compounds represented by Chemical Formulas 1 to 12 or optical isomers thereof.
  • Pharmaceutically acceptable carriers are commonly used in the art, and specifically lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, Polyvinylpyrrolidine, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, mineral, or oil may be, but is not limited thereto.
  • compositions of the present invention may further include lubricants, wetting agents, sweetening agents, flavoring agents, emulsifying agents, suspending agents, preservatives, dispersing agents, stabilizers, and the like in addition to the above components.
  • pharmaceutical composition of the present invention uses pharmaceutically acceptable carriers and excipients for oral dosage forms such as tablets, powders, granules, pills, capsules, suspensions, emulsions, solutions, emulsions, syrups, external preparations, suppositories, etc.
  • it may be formulated in the form of a sterile injectable solution and prepared in a unit dosage form, or may be prepared by being placed in a multi-dose container.
  • the formulation may be prepared by a conventional method used for formulation in the art or a method disclosed in Remington's Pharmaceutical Science (19 th ed., 1995), and may be formulated into various formulations according to each disease or ingredient.
  • the pharmaceutical composition of the present invention may be administered orally or parenterally administered according to a desired method, and may preferably be administered orally, but is not limited thereto.
  • the dosage of the pharmaceutical composition of the present invention varies depending on factors such as formulation method, administration mode, patient's age, weight, sex, pathological condition, dietary intake type, administration route, excretion rate, and response sensitivity. can do.
  • a preferred dosage of the pharmaceutical composition of the present invention is 1 mg/kg to 1000 mg/kg on an adult basis, and may be administered once to several times a day.
  • the present invention provides a method for preventing or treating obesity or metabolic diseases comprising administering the pharmaceutical composition to an individual.
  • administration means introducing a given substance to an individual in an appropriate manner.
  • mice refers to all animals such as mice, mice, livestock, etc., including humans that have or may develop disease, and may specifically be mammals including humans, but is not limited thereto. .
  • the method of preventing or treating obesity or metabolic disease of the present invention may be administering the pharmaceutical composition in a pharmaceutically effective amount.
  • the term "pharmaceutically effective amount” refers to an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment and not cause side effects, which is the sex, age, and weight of the patient. , Health condition, type of disease, severity, drug activity, sensitivity to drugs, method of administration, time of administration, route of administration, and rate of excretion, duration of treatment, factors including drugs used in combination or simultaneously, and other medical fields. It can be determined by a person skilled in the art according to known factors.
  • the present invention provides a food composition for preventing or improving obesity or metabolic diseases comprising any one or more of a compound represented by the following Chemical Formulas 1 to 12 or optical isomers thereof as an active ingredient.
  • improvement refers to any action in which a disease is improved or beneficially altered by administration of the composition.
  • the term "food” refers to meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages , Vitamin complexes, health functional foods, health foods, and health supplements, and all foods in the usual sense are included.
  • the term "functional food” is the same term as food for special health use (FoSHU). In addition to supplying nutrients, the processed medicine and medical effects are effective so that the biological control function is effectively displayed. Means high food.
  • the term'function (sex)' means to control nutrients for the structure and function of the human body or to obtain useful effects for health purposes such as physiological actions.
  • health food refers to a food having an active health maintenance or enhancement effect compared to general food
  • health supplement food refers to a food for the purpose of health supplementation.
  • health functional food, health food, and health supplement food are used interchangeably.
  • the food of the present invention can be prepared by a method commonly used in the art, and during the production, raw materials and ingredients commonly added in the art may be added to prepare the food product. Specifically, proteins, carbohydrates, fats, nutrients, flavoring agents, and flavoring agents may be included, and examples of the carbohydrates are glucose, fructose, maltose, sucrose, oligosaccharide, dextrin, cyclodextrin, xylitol, sorbitol, ery Troll, saccharin, or synthetic flavoring agents, but are not limited thereto.
  • the food composition of the present invention may be prepared in various forms without limitation, provided that it is a formulation recognized as a food.
  • the present invention provides a feed composition for preventing or improving obesity or metabolic diseases comprising any one or more of a compound represented by the following Chemical Formulas 1 to 12 or optical isomers thereof as an active ingredient.
  • feed of the present invention means any natural or artificial diet, one meal meal, etc., or a component of the one meal meal for consumption and digestion by livestock.
  • the feed may contain feed additives or auxiliary feeds.
  • the kind of feed is not particularly limited, and feed commonly used in the art may be used.
  • Non-limiting examples of the feed include vegetable feeds such as grains, root fruits, food processing by-products, algae, fiber, pharmaceutical by-products, oils and fats, starches, meals or grain by-products; Animal feeds such as proteins, inorganic logistics, oils and fats, minerals, oils and fats, single-cell proteins, zooplanktons or foods. These may be used alone or in combination of two or more.
  • the present invention provides a use of a compound represented by the following Formulas 1 to 12 or an optical isomer thereof for the prevention or treatment of obesity or metabolic diseases.
  • the present invention provides the use of a compound represented by the following Formulas 1 to 12 or an optical isomer thereof for the manufacture of a medicament for preventing or treating obesity or metabolic diseases.
  • novel sesqueterpene derivatives or optical isomers thereof of the present invention not only reduce body weight and visceral fat mass, but also have the effect of reducing plasma total cholesterol, triglyceride, blood sugar, insulin concentration, and triglyceride concentration in hepatic tissue. It can be usefully used in the prevention or treatment of metabolic diseases.
  • 1 is an image showing the fat content of the nematode after treatment of the novel sesquiterpene derivative of the present invention by concentration.
  • the numerical value in the image indicates the fat content colored in the composition and the lower the value (+1) the fat content The lower the number and the higher the value (+4), the higher the fat content.
  • Figure 2 is a graph showing the fat content of nematodes after treatment of the novel sesquiterpene derivative of the present invention by concentration, the X-axis of the graph is the sample concentration ( ⁇ g/ml) and the Y-axis is the fat content (+1 to +4). Means).
  • the crude crystal compound was recrystallized by adding hexane and the labeled compound (3R,3aS,6R,7R,8aS)-3,6,8,8-tetramethyloctahydro-1H-3a,7-methanoazulen-6-yl 17.6 g (85%) of -4-acetoxy-3-methoxybenzoate was obtained.
  • the crude crystal compound was recrystallized by adding hexane and the labeled compound (E)-(3R,3aS,6R,7R,8aS)-3,6,8,8-tetramethyloctahydro-1H-3a,7-methanoazulene -6-yl-3-(4-(2-hydroxyethoxy)phenyl)acrylate 13.6g (66%) was obtained.
  • the crude crystal compound was recrystallized by adding hexane and the labeled compound (E)-(3R,3aS,6R,7R,8aS)-3,6,8,8-tetramethyloctahydro-1H-3a,7-methanoazulene -6-yl-3-(4-(2-(dimethylamino)ethoxy)phenyl)acrylate 16.7g (76%) was obtained.
  • a rosewood fraction sample was added to the liquid medium containing the nematode nematode and incubated by rotating at 100 rpm in a dark room at a room temperature of 15 °C to 20 °C.
  • the sample was dissolved in DMSO and added to the culture medium, and the final concentration of DMSO was 1% or less. 1% DMSO had no effect on the lipid synthesis and growth of the nematode.
  • 10 ug/ml of Nile Red reagent 30 ⁇ l was added to adjust the final concentration of Nile Red to 100 ⁇ g/ml, and rotation culture was continued for 2 days.
  • the movement was stopped by dropwise adding 20 ⁇ l of 0.3% NaN 3 to a slide glass, adding Nile Red to it, and adding 100 ⁇ l of a nematode solution cultured for 2 days.
  • Adipocytes of the nematode nematode that emit red fluorescence in a dark room were photographed using a luminescent microscope, and the fat content was measured. The lowest fat content was expressed as +1 (high activity), and the fat content was expressed as +4 (low activity).
  • the compounds of the present invention exhibit excellent anti-obesity efficacy, from which it was found that the novel sesquiterpene derivative of the present invention can be usefully used as a treatment for obesity.
  • the obesity-induced diet used in this experiment was a high fat diet; HFD, 40% fat calorie: 17g pig oil lard + 3% corn oil/100g diet], and the diet containing the novel sesquiterpene derivative of the present invention is prepared in the same composition as HFD, but the compound is 0.5% It was prepared to contain at the level.
  • the composition of the experimental diet is as shown in Table 1 below.
  • 6-week-old male (male) C57BL/6J mice were adapted to the experimental environment for 1 week with solid feed (after acclimatization), followed by a high fat diet control group and a novel sesquiterpene derivative of the present invention according to the randomized block method. It was randomly placed as a dietary experimental group including and reared for a total of 6 weeks. Diet was supplied with water between 10 and 11 am every day, and dietary intake was measured daily and once every 3 days.
  • Table 2 shows the change in body weight of mice after feeding the experimental diet for 8 weeks.
  • the weight of the diet experiment group containing the novel sesquiterpene derivative of the present invention was about 40% to 80% compared to the weight of the high fat diet (HFD) control group, all of which were significantly reduced. (P ⁇ 0.05).
  • the visceral fat mass of the included diet experiment group was about 25% to 60% compared to the visceral fat mass of the high fat diet (HFD) control group, and all were significantly reduced (P ⁇ 0.05).
  • Plasma total cholesterol, triglyceride, and glucose concentrations were measured twice each using a commercially available measurement kit (Bio-clinical system), and insulin concentration was measured by ELISA using a mouse insulin kit (Shibayaki Japan).
  • the lipid component of liver tissue was extracted according to the method of Folch et al. After adding 1 ml of distilled water to 0.25 g of liver tissue, it was homogenized using a polytron homogenizer (IKA-WERKE GmH & Co., Germany). Dichloromethane: methanol solution (2:1 v/v) 5 mL was added to the homogenate, mixed well, centrifuged for 10 minutes (1000 rpm) to separate the lower layer solution, and then added to the upper layer solution.
  • Table 3 shows the changes in plasma total cholesterol, triglyceride, glucose and insulin concentrations, IRI (insulin resistance index), and the content of triglyceride in the liver after feeding the experimental diet for 8 weeks.
  • IRI insulin resistance index
  • the plasma total cholesterol concentration of the diet experiment group containing the novel sesquiterpene derivative of the present invention was significantly reduced compared to the plasma total cholesterol concentration of the high fat diet (HFD) control group.
  • the plasma triglyceride concentration of the dietary experimental group containing the novel sesquiterpene derivative of the present invention was significantly reduced compared to the plasma triglyceride concentration of the high fat diet (HFD) control group.
  • novel sesquiterpene derivative of the present invention can be usefully used in the prevention, alleviation, amelioration or treatment of hyperlipidemia.
  • the concentration of triglycerides in liver tissues of the dietary experimental group containing the novel sesquiterpene derivatives of the present invention was significantly reduced compared to the concentrations of hepatic triglycerides in the high fat diet (HFD) control group. .
  • novel sesquiterpene derivatives of the present invention can be usefully used in the prevention, alleviation, improvement or treatment of fatty liver.
  • the fasting blood glucose of the dietary experimental group containing the novel sesquiterpene derivative of the present invention was significantly decreased compared to the fasting blood glucose of the high fat diet (HFD) control group.
  • the insulin concentration of the dietary experimental group containing the novel sesquiterpene derivative of the present invention was significantly decreased compared to the insulin concentration of the high fat diet (HFD) control group.
  • the insulin resistance index (IRI) of the diet experiment group containing the novel sesquiterpene derivative of the present invention was significantly reduced compared to the insulin resistance index of the control group on a high fat diet.
  • novel sesquiterpene derivatives of the present invention can be usefully used in preventing, alleviating, improving or treating diabetes, and improving insulin resistance.

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Abstract

La présente invention concerne un nouveau dérivé de sesquiterpène et son utilisation et, plus particulièrement, un nouveau dérivé de sesquiterpène ou un isomère optique de celui-ci, une composition pharmaceutique, une composition alimentaire et une composition alimentaire le comprenant, et leur utilisation pour la prévention ou le traitement de l'obésité ou d'une maladie métabolique.
PCT/KR2020/011066 2019-08-20 2020-08-19 Nouveau dérivé de sesquiterpène et son utilisation Ceased WO2021034111A1 (fr)

Applications Claiming Priority (2)

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