WO2019103248A1 - Composition pour prévenir ou traiter l'athérosclérose, contenant un extrait de dystaenia takeshimana - Google Patents

Composition pour prévenir ou traiter l'athérosclérose, contenant un extrait de dystaenia takeshimana Download PDF

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Publication number
WO2019103248A1
WO2019103248A1 PCT/KR2018/003931 KR2018003931W WO2019103248A1 WO 2019103248 A1 WO2019103248 A1 WO 2019103248A1 KR 2018003931 W KR2018003931 W KR 2018003931W WO 2019103248 A1 WO2019103248 A1 WO 2019103248A1
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extract
composition
preventing
present
macrophages
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PCT/KR2018/003931
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English (en)
Korean (ko)
Inventor
판철호
권재영
김다혜
윤계윤
김성훈
권학철
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한국과학기술연구원
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Publication of WO2019103248A1 publication Critical patent/WO2019103248A1/fr

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    • 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
    • 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)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232—Angelica
    • 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
    • A23V2200/326—Foods, ingredients or supplements having a functional effect on health having effect on cardiovascular health

Definitions

  • the present invention relates to a composition for the prevention or treatment of atherosclerosis, which comprises an extract of a sea bream.
  • the present invention relates to a pharmaceutical composition, a food composition, a preventive or therapeutic agent for atherosclerosis, a composition for preventing or treating atherosclerosis, And a composition for inhibiting macrophage death by triglyceride.
  • Atherosclerosis sometimes referred to as atherosclerosis, is a disease in which hypertrophy or tissue degeneration occurs in the arterial wall. As the inner wall of the artery thickens and the inside diameter narrows, obstacles appear in the blood stream supplying oxygen and various nutrients, thereby causing various diseases. Arteriosclerosis is prone to develop in the cerebral arteries or coronary arteries. In the case of cerebral artery sclerosis, headache, dizziness, mental disorder and cerebral edema are the causes. In the case of coronary artery sclerosis, it causes pain and arrhythmia in the heart, causing angina and myocardial infarction.
  • arteriosclerosis is closely related to the development and progression of diseases such as obesity (overweight), thrombosis, hypercoagulability, and thrombotic conditions (arterial and venous), including metabolic syndrome and lipidemia, including central obesity, Causes or aggravates chronic complications.
  • diseases such as obesity (overweight), thrombosis, hypercoagulability, and thrombotic conditions (arterial and venous), including metabolic syndrome and lipidemia, including central obesity, Causes or aggravates chronic complications.
  • Such atherosclerosis is caused by excessive cell proliferation in the inner lining of the artery, resulting in atheroma, fibrosis around the atheroma, and progress of the blood vessels becoming harder.
  • Specific mechanisms of onset are as follows. First, the monocytes are differentiated into macrophages, and the differentiated macrophages become dead or foam cells by digesting HDL / LDL-cholesterol or triglycerides. The resulting bubble cells continue to induce inflammatory responses. Over time, the bubble cells are killed by apoptosis and the killed cells are removed by newly migrating macrophages.
  • the ratio of macrophages to bubble cells or death due to triglycerides increases. That is, as the macrophages die, their immune function and triglyceride metabolism are lowered, and the function of removing the formed foam cells is lowered, thereby increasing the possibility that arteriosclerosis develops or deteriorates. Therefore, in order to prevent the onset or deterioration of arteriosclerosis, it is important to keep the macrophage functioning to remove the foam cells even when the blood fat concentration is high, or to minimize the killing by the triglyceride.
  • statins such as rosuvastatin and simvastatin are mainly used for the treatment of arteriosclerosis, but it is known that there is a side effect of reducing the activity of macrophages that remove foam cells.
  • a statin drug causes side effects such as diabetes, muscular dystrophy and hyperglycemia, and it is necessary to study natural products having less side effects.
  • a composition for treating arteriosclerosis containing an extract of Robinia pseudo-acacia tree (Korean Patent Laid-Open No. 10-2016-0084990), an anti-hyperlipemia and an anti-arteriosclerotic composition comprising a fermented extract of cinnamon ginseng (Korean Patent Laid- (Korean Patent Registration No. 10-1516764), a composition for preventing or treating atherosclerosis, including a horseradish peroxidase, and a composition for preventing or treating arteriosclerosis using a natural substance, such as a composition for preventing or treating atherosclerosis,
  • the island ( Angelica takeshimana ) is a perennial herbaceous plant belonging to the genus Porphyra , also called pork paste. It is a perennial plant that grows up to about 2m tall. The stem is hollow and leaves are alternate. It grows on Ulleungdo as a Korean species. These islands are believed to be effective against atopic dermatitis because they suppress the activation and expression of inflammatory factors. However, the effects associated with arteriosclerosis have not been known.
  • the present inventors have made intensive efforts to develop a natural substance exhibiting a preventive or therapeutic effect on arteriosclerosis, and as a result, it has been confirmed that the islet extract has an effect of inhibiting the death of macrophages caused by triglycerides, thus completing the present invention .
  • Another object of the present invention is to provide a method for the prevention or treatment of arteriosclerosis comprising the step of administering the composition to a subject.
  • composition comprising the extract of the present invention can maintain the function of macrophages even when the concentration of blood lipids is high, and thus can be usefully used for the prevention or treatment of atherosclerosis caused by a decrease in macrophage function.
  • FIG. 1 is a graph showing an effect of inhibiting the death of macrophages by triglyceride of an ethanol extract of islets according to an embodiment of the present invention.
  • Cell viability was expressed as normal control (control).
  • TG means triglyceride.
  • FIG. 2 is a graph showing an effect of inhibiting the death of macrophages by triglyceride of a methanol extract of islets according to an embodiment of the present invention.
  • FIG. Cell viability was expressed as normal control (control).
  • TG means triglyceride.
  • One aspect of the present invention provides a pharmaceutical composition for preventing or treating atherosclerosis, comprising an extract of a sea bream or a fraction thereof as an active ingredient.
  • the islet extract or its fractions have an effect of preventing or ameliorating atherosclerosis, or preventing or preventing atherosclerosis, by confirming that the islet extract has an effect of inhibiting the death of macrophages caused by triglycerides, And it can be used for treatment.
  • islands of the present invention means a plant having the scientific name of Angelica takeshimana .
  • the island is a perennial plant that grows up to 2 meters tall. It has been known that inhibition of the activation and expression of inflammatory factors is effective for atopic dermatitis. However, the effect on arteriosclerosis is not known, and it was first described by the present inventors.
  • the outpost of the above-mentioned islands may be used for the prevention or treatment of arteriosclerosis, and specifically, leaves, stems, flowers, roots or a combination thereof may be used, but the present invention is not limited thereto as long as it has an effect of preventing or treating arteriosclerosis.
  • the above-mentioned island can be purchased commercially, sold or cultivated in nature.
  • extract of the present invention includes the extract obtained by extracting the island, the diluted or concentrated solution of the extract, the dried product obtained by drying the extract, the adjusted product or the purified product of the extracted solution, And extracts of all formulations which can be formed using extracts.
  • the method for extracting the above-mentioned islands is not particularly limited, and can be extracted according to a method commonly used in the art.
  • Non-limiting examples of the extraction method include hydrothermal extraction, ultrasonic extraction, filtration, and reflux extraction. These may be performed alone or in combination with two or more methods.
  • the type of the extraction solvent used for extracting the above-mentioned islands is not particularly limited, and any solvent known in the art can be used.
  • Nonlimiting examples of the extraction solvent include water, alcohols having 1 to 4 carbon atoms, and mixed solvents thereof. These solvents may be used alone or in combination. Specifically, ethanol or methanol may be used, and the methanol may be 10-100% (v / v), more specifically 70-100% (v / v) methanol, but is not limited thereto.
  • the islet extract may be an ethanol or methanol extract of a sultan.
  • fraction of the present invention means a product obtained by performing fractionation to separate a specific component or a specific component group from a mixture containing various components.
  • the fractionation method for obtaining the fraction of the above-mentioned islands extract is not particularly limited and may be carried out according to a method commonly used in the art.
  • Non-limiting examples of the fractionation method include a solvent fractionation method performed by treating various solvents, an ultrafiltration fractionation method performed through an ultrafiltration membrane having a constant molecular weight cut-off value, various chromatography (size, charge, hydrophobicity Or affinity-based separation), and a combination thereof, and the like.
  • the extract of the present invention can be obtained by treating a predetermined solvent with an extract obtained by extracting the island of the present invention to obtain a fraction from the extract.
  • the kind of the fraction solvent used for obtaining the fraction in the present invention is not particularly limited, and any solvent known in the art can be used.
  • Non-limiting examples of the fraction solvent include polar solvents such as water and alcohols having 1 to 4 carbon atoms; Non-polar solvents such as hexane (Hexan) and ethyl acetate (Ethyl acetate); Or a mixed solvent thereof. These may be used alone or in combination of one or more, but the present invention is not limited thereto.
  • extract or fraction may be prepared and used in the form of a dry powder after extraction, but is not limited thereto.
  • arteriosclerosis of the present invention means a disease in which blood vessels become narrowed or clogged, causing the blood vessels to cause peripheral blood flow disorders.
  • the arteriosclerosis is also called atherosclerosis.
  • Atherosclerosis can be caused by macrophage-mediated elimination of HDL / LDL-cholesterol or triglycerides in the blood.
  • macrophages are converted into bubble cells by phagocytosing HDL / LDL-cholesterol or triglycerides. If the bubble cells are not removed by macrophages, they may cause a continuous inflammatory reaction, resulting in the development or worsening of atherosclerosis. Therefore, maintenance or maintenance of macrophage function is essential for prevention or treatment of arteriosclerosis.
  • the islet extract may inhibit the death of macrophages by triglycerides.
  • the above-mentioned islands extract has an effect of inhibiting the death of macrophages that cause the onset or aggravation of arteriosclerosis, and thus can be used for the prevention or treatment of arteriosclerosis.
  • prophylactic of the present invention refers to any act that inhibits or delays arteriosclerosis by administration of a composition comprising the above-mentioned sumbird extract or fractions thereof.
  • treatment refers to any action that improves or alters the symptoms of arteriosclerosis by administration of a composition comprising the above-mentioned isabide extract.
  • the islet ethanol or methanol extract can increase the survival rate of macrophages by inhibiting the death of macrophages by triglycerides (FIGS. 1 and 2).
  • composition of the present invention containing the above extract may be useful for the prevention or treatment of arteriosclerosis because the above-mentioned extract of the present invention can maintain the function of the macrophage even in a state of high blood fat concentration .
  • the pharmaceutical composition of the present invention may include, but is not limited to, 0.001 to 80, specifically 0.001 to 70, more specifically 0.001 to 60% by weight of the above-mentioned sumbird extract or fraction thereof, based on the total weight of the composition.
  • the pharmaceutical composition may further comprise a pharmaceutically acceptable carrier, excipient or diluent conventionally used in the manufacture of a pharmaceutical composition, which carrier comprises a non-naturally occuring carrier can do.
  • a pharmaceutically acceptable carrier excipient or diluent conventionally used in the manufacture of a pharmaceutical composition, which carrier comprises a non-naturally occuring carrier can do.
  • the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, But are not limited to, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil.
  • each of the pharmaceutical compositions may be formulated into tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, sterilized aqueous solutions, nonaqueous solutions, suspensions, emulsions, , And may be oral or parenteral formulations of various types.
  • a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used.
  • the solid preparation for oral administration may be a tablet, a pill, a powder, a granule, a capsule, etc.
  • the solid preparation may contain at least one excipient such as starch, calcium carbonate, sucrose or lactose, Gelatin and the like may be used.
  • excipients such as starch, calcium carbonate, sucrose or lactose, Gelatin and the like may be used.
  • lubricants such as magnesium stearate, talc, and the like may be used.
  • As the liquid preparation for oral administration suspensions, solutions, emulsions, syrups and the like may be used.
  • various excipients such as wetting agents, sweeteners, Can be used.
  • sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations or suppositories may be used.
  • non-aqueous solvent and the suspending agent examples include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate.
  • injectable ester such as ethyl oleate.
  • suppositories include, but are not limited to, witepsol, macrogol, tween 61, cacao butter, laurin, and glycerogelatin.
  • Another aspect provides a method of preventing or treating arteriosclerosis comprising administering the composition to a subject.
  • administering means introducing the pharmaceutical composition into a subject in an appropriate manner.
  • individual of the present invention means all animals such as mice, mice, livestock, etc., including humans who have developed or can develop arteriosclerosis.
  • the animal may be, but is not limited to, a mammal such as a cow, a horse, a sheep, a pig, a goat, a camel, a nutrient, a dog, or a cat, which requires prevention or treatment of similar symptoms.
  • the pharmaceutical composition of the present invention may be administered in a pharmaceutically effective amount.
  • pharmaceutically effective amount means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level will depend on the species and severity, age, sex, The sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts.
  • the pharmaceutical composition may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. In addition, it can be administered singly or multiply. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without side effects, which can be easily determined by a person skilled in the art.
  • the pharmaceutical composition may be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically) depending on the intended method, and the dose may be determined depending on the condition and the weight of the patient, The mode of administration, the route of administration, and the time, but may be appropriately selected by those skilled in the art.
  • the pharmaceutical composition may be administered in an amount of generally 0.001 to 1000 mg / kg, more particularly 0.05 to 200 mg / kg, most specifically 0.1 to 100 mg / kg,
  • the desired dosage can be suitably selected by those skilled in the art depending on the condition and the weight of the individual, the degree of disease, the drug form, the administration route and the period.
  • Another aspect provides a food composition for preventing or ameliorating atherosclerosis, which comprises an islet extract or a fraction thereof as an active ingredient.
  • the food composition of the present invention can be ingested routinely and unlike ordinary medicines, it has a merit that there is no side effect that may occur when a natural product is used as a raw material for a long time, and therefore, it is very useful for prevention or improvement of arteriosclerosis Lt; / RTI >
  • improvement means any action that reduces the degree of a parameter associated with a condition to be treated, such as a symptom, by the ingestion of the food composition.
  • food of the present invention includes dairy products such as meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen and other noodles, gums, ice cream, various soups, drinks, tea, , A vitamin complex, a health functional food, and a health food, all of which include foods in a conventional sense.
  • the health functional food is the same term as food for special health use (FoSHU).
  • the health functional food has a high medical effect, It means food.
  • 'function (sex)' refers to the structure and function of the human body to obtain nutritional effects or obtain a beneficial effect for health use such as physiological action.
  • the health food refers to a food having an active health promotion or promotion effect compared with a general food, and a health supplement food refers to a food for health assistance.
  • the terms health functional foods, health foods, and health supplements may be used.
  • the health functional food is a food prepared by adding the extract of the present invention or a fraction thereof to a food material such as a beverage, a tea, a spice, a gum, or a confection, or by preparing an encapsulation, a powder or a suspension,
  • a food material such as a beverage, a tea, a spice, a gum, or a confection
  • a food material such as a beverage, a tea, a spice, a gum, or a confection
  • preparing an encapsulation, a powder or a suspension unlike general medicines, there is an advantage that there is no side effect that can occur when a drug is taken for a long time by using the food as a raw material.
  • the food of the present invention can be prepared by a method commonly used in the art, and can be prepared by adding raw materials and components which are conventionally added in the art.
  • the food composition can be produced in various forms without limitations as long as it is a food-acceptable formulation.
  • the food composition may further comprise a physiologically acceptable carrier.
  • the carrier is not particularly limited and any carrier conventionally used in the art can be used.
  • the food composition may contain additional components that are commonly used in food compositions and can improve odor, taste, visual appearance, and the like.
  • Minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu) and chromium (Cr); And amino acids such as lysine, tryptophan, cysteine, valine, and the like.
  • the food composition may contain at least one kind selected from the group consisting of preservatives (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate), disinfectants (such as bleaching powder and highly bleached white powder, sodium hypochlorite), antioxidants (butylhydroxyanisole (BHA) (Sodium nitrite), bleach (sodium sulfite), seasoning (sodium MSG glutamate, etc.), sweeteners (dicin, cyclamate, saccharin, etc.), coloring agents , Sodium, etc.), perfume (vanillin, lactones, etc.), swelling agents (alum, potassium hydrogen D-tartrate), emulsifiers, thickeners (foams), encapsulating agents, gum bases, foam inhibitors, solvents, And may include food additives.
  • the additives can be selected according to the type of food and used in an appropriate amount.
  • compositions for inhibiting macrophage death by triglycerides comprising an extract of the island or a fraction thereof as an active ingredient.
  • macrophage death by triglycerides means that macrophage function is lost or damaged by triglyceride, and macrophages are necrosis, apoptosis, And the conversion of phagocytes to other types of different cells.
  • the macrophage removes various substances unnecessary for the human body such as the triglyceride and dead cells.
  • the inflammation reaction is caused by the above-mentioned substances, and a disease such as atherosclerosis may develop. Therefore, macrophage death caused by triglycerides can also be useful for preventing or treating diseases caused by macrophage death caused by triglycerides such as arteriosclerosis.
  • the extract of the sea bass can inhibit the death of macrophages by triglycerides and increase the survival rate of macrophages (Fig. 1).
  • the composition of the present invention containing the extract can be effectively used for inhibiting macrophage death by triglycerides It is suggestive.
  • a human mononuclear cell line THP-1 was inoculated into a 96-well plate at a number of 1.5 ⁇ 10 4 cells / well, treated with 200 nM phorbol-12-myristate-13-acetate for 24 hours, Differentiation was induced.
  • the differentiated macrophages were maintained in RPMI medium containing 1% penicillin-streptomycin and 10% fetal bovine serum at 37 ° C under 5% carbon dioxide and treated with 0.2-2 ⁇ l / ml of the islet extract for 24 hours Respectively.
  • the cells were then washed twice with DPBS and treated with triglyceride (TG) at a concentration of 1 mg / ml for 24 hours.
  • TG triglyceride
  • the survival rate of macrophages reduced by the triglyceride was increased in the case of treatment with the methanol extract of the island. Specifically, 70, 90 or 100% (v / v) It was confirmed that the extract had a better survival rate increase effect than that extracted with 10, 30 or 50% (v / v) methanol extract.
  • the extract of the sea bass effectively inhibits the death of macrophages due to triglycerides, thereby suppressing the immune function, the degradation of triglyceride metabolism, the formation of foam cells, and the deterioration of the formed foam cells due to the macrophage death
  • the extract of the sea bass effectively inhibits the death of macrophages due to triglycerides, thereby suppressing the immune function, the degradation of triglyceride metabolism, the formation of foam cells, and the deterioration of the formed foam cells due to the macrophage death

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Abstract

La présente invention concerne une composition pour prévenir ou traiter l'athérosclérose, contenant un extrait de Dystaenia takeshimana et une composition pharmaceutique pour prévenir ou traiter l'athérosclérose et une composition alimentaire, qui contiennent, en tant que principe actif, un extrait de Dystaenia takeshimana ou une fraction correspondante ; un procédé pour prévenir ou traiter l'athérosclérose ; et une composition pour inhiber la mort cellulaire des macrophages induite par les triglycérides. Une composition contenant un extrait de Dystaenia takeshimana de la présente invention permet de maintenir les fonctions des macrophages même dans un état dans lequel la concentration en graisse sanguine est élevée, ce qui permet d'être efficacement utilisable pour prévenir ou traiter l'athérosclérose provoquée par un fonctionnement réduit de macrophages.
PCT/KR2018/003931 2017-11-21 2018-04-03 Composition pour prévenir ou traiter l'athérosclérose, contenant un extrait de dystaenia takeshimana WO2019103248A1 (fr)

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KR1020170155769A KR102006310B1 (ko) 2017-11-21 2017-11-21 섬바디 추출물을 포함하는 동맥경화증의 예방 또는 치료용 조성물
KR10-2017-0155769 2017-11-21

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KR102214557B1 (ko) 2019-07-03 2021-02-10 계명대학교 산학협력단 섬바디 추출물을 유효성분으로 함유하는 화장료 조성물

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ZHANG, B, -C. ET AL.: "Luteolin attenuates foam cell formation and apoptosis in Ox-LDL-stimulated macrophages by enhancing autophagy", CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, vol. 39, no. 53, 2016, pages 2065 - 2076, XP055619354 *

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