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WO2018174502A1 - Composition pharmaceutique pour le traitement prophylactique ou thérapeutique du diabète comprenant un extrait de feuille de chrysanthème en tant que principe actif - Google Patents

Composition pharmaceutique pour le traitement prophylactique ou thérapeutique du diabète comprenant un extrait de feuille de chrysanthème en tant que principe actif Download PDF

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Publication number
WO2018174502A1
WO2018174502A1 PCT/KR2018/003191 KR2018003191W WO2018174502A1 WO 2018174502 A1 WO2018174502 A1 WO 2018174502A1 KR 2018003191 W KR2018003191 W KR 2018003191W WO 2018174502 A1 WO2018174502 A1 WO 2018174502A1
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WO
WIPO (PCT)
Prior art keywords
leaf extract
chrysanthemum leaf
chrysanthemum
preventing
composition
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/KR2018/003191
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English (en)
Korean (ko)
Inventor
최명숙
김예진
권은영
류리
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.)
Industry Academic Cooperation Foundation of KNU
Original Assignee
Industry Academic Cooperation Foundation of KNU
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
Priority claimed from KR1020170139264A external-priority patent/KR20180106823A/ko
Application filed by Industry Academic Cooperation Foundation of KNU filed Critical Industry Academic Cooperation Foundation of KNU
Publication of WO2018174502A1 publication Critical patent/WO2018174502A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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 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
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/287—Chrysanthemum, e.g. daisy

Definitions

  • the present invention relates to a pharmaceutical composition for preventing or treating diabetes comprising chrysanthemum leaf extract as an active ingredient, and more particularly to a composition for preventing, treating and improving diabetes comprising chrysanthemum leaf extract as an active ingredient. .
  • Fat cells There are about 20 billion fat cells in the human body, which are responsible for accumulating or releasing energy in mammals. Fat cells store the energy consumed and stored in the form of triglycerides, and then break it down into free fatty acids and glucose when energy is depleted.
  • Diabetes one of the diseases caused by fat accumulation as described above, is a disease in which glucose present in the blood is discharged through urine, and is one of chronic degenerative diseases that are not fundamentally cured.
  • diabetes In modern times, due to changes in diet and lack of exercise, a great change occurred in the body's own energy metabolism process, resulting in an increase in chronic degenerative diseases such as diabetes.
  • the prevalence of diabetes In Korea, the prevalence of diabetes is known to reach 5 to 10% and shows a continual increase. In the United States, diabetes has increased six-fold over the past 40 years, and the increase has led to the number of patients reaching 20 million by 2050. It is expected to lead to death.
  • Type 1 diabetes insulin-dependent diabetes
  • type 2 diabetes insulin-independent diabetes
  • MRDM malnutrition diabetes
  • Type 2 diabetes which accounts for more than 90% of diabetic patients in Korea, is hyperglycemic. Metabolic disease characterized by the fact that genetic, metabolic, environmental factors caused by the decrease in insulin secretion of pancreatic beta cells or increased insulin resistance in peripheral tissues has been reported. In this regard, it is known that insulin sensitivity is decreased when body fat increases with diabetes mellitus, and abdominal fat accumulation is known to be related to glucose intolerance. In addition, since diabetes mellitus and insulin resistance have a close correlation in patients with type 2 diabetes, it is known that the more severe diabetes mellitus, the greater the insulin resistance. In addition, the pathogenesis of insulin independent diabetes mellitus (type 2 diabetes) is known as a complex disorder of insulin secretion and insulin resistance. Diabetes mellitus is a disease with chronic hyperglycemia due to this complex disorder.
  • insulin secretion disorder refers to a situation in which the proper amount of insulin is not secreted from the beta cells of the pancreas according to the blood glucose concentration, which includes both a quantitative decrease in the secretion of insulin secreting cells and a functional secretion disorder.
  • Insulin resistance refers to a situation in which secreted insulin has reached the target organ in the bloodstream but its insulin action and sensitivity are degraded in the target cell, which is generally considered to be a signaling disorder after cell membrane receptor binding, and is a cause of genetic predisposition.
  • Diabetes decreased physical activity and hyperglycemia or dyslipidemia. Insulin resistance requires higher levels of insulin to overcome resistance, and conversely, hyperglycemia caused by insufficient insulin secretion may worsen insulin resistance again.
  • the chrysanthemum is a flower that for perennial plants of chrysanthemum, chrysanthemum extract, antioxidant and anti-inflammatory effects that are known but (Korea Patent Publication No. 2010-033573), chrysanthemum leaves (Chrysanthemum morifolium Ramat leaf) belongs to the Asteraceae Efficacy is not clear.
  • the present inventors while devoting to research on the development of a material having anti-diabetic effect, confirmed that chrysanthemum leaf extract can regulate blood sugar and improve insulin resistance, and completed the present invention based on this.
  • An object of the present invention is to provide a pharmaceutical composition for preventing or treating diabetes, including chrysanthemum leaf extract as an active ingredient.
  • Another object of the present invention is to provide a health functional food composition for preventing or improving diabetes, including chrysanthemum leaf extract as an active ingredient.
  • the present invention provides a pharmaceutical composition for preventing or treating diabetes, including chrysanthemum leaf extract as an active ingredient.
  • the composition controls blood sugar and improves insulin resistance, and the composition may lower blood sugar in the body and reduce insulin levels, thereby improving insulin resistance.
  • the chrysanthemum leaf extract is water, lower alcohols of C1 to C4, n-hexane, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, and mixed solvents thereof It may be extracted with a solvent selected from the group consisting of.
  • the present invention provides a health functional food composition for preventing or improving diabetes, including chrysanthemum leaf extract as an active ingredient.
  • the present invention also provides a pharmaceutical composition for treating or preventing insulin resistance-related diseases, including chrysanthemum leaf extract as an active ingredient.
  • the present invention also provides a health functional food composition for preventing or improving insulin resistance-related diseases, including chrysanthemum leaf extract as an active ingredient.
  • the present invention provides a method for preventing or treating diabetes, comprising administering the composition to a subject.
  • the effect of improving the blood glucose control and insulin resistance of the composition comprising the chrysanthemum leaf extract as an active ingredient it was confirmed that it can be used as an active ingredient for the prevention, improvement or treatment of diabetes.
  • the pharmaceutical composition according to the present invention may include a pharmaceutically acceptable carrier in addition to the active ingredient.
  • the pharmaceutically acceptable carrier is commonly used in the formulation, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose , Polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate and mineral oil, and the like.
  • it may further include a lubricant, wetting agent, sweetener, flavoring agent, emulsifier, suspending agent, preservative and the like.
  • compositions of the present invention can be administered orally or parenterally (eg, applied intravenously, subcutaneously, intraperitoneally or topically) according to the desired method, and the dosage is determined by the condition and weight of the patient, Depending on the extent, drug form, route of administration, and time, it may be appropriately selected by those skilled in the art.
  • the pharmaceutical composition of the present invention is 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 refers to the type of disease, the severity, the activity of the drug, It may be determined according to the sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of treatment, factors including the drug used concurrently and other factors well known in the medical field.
  • the pharmaceutical compositions according to the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be single or multiple administrations. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect in a minimum amount without side effects, which can be easily determined by those skilled in the art.
  • “individual” means a subject in need of a method for preventing, controlling or treating a disease, and more specifically, a primate, mouse, rat, dog, or cat, which is human or non-human. Means mammals, such as horses and cattle.
  • Chrysanthemum morifolium Ramat leaf was pulverized for easy extraction, and 70% ethanol was added to 10 kg of chrysanthemum leaves for 2 hours at 65-75 °C, and the number of extraction was 3 times.
  • the extract was concentrated and spray dried at 120 ° C. and the yield of chrysanthemum leaf extract was calculated to be 17.4%.
  • mice were fasted for 12 hours at week 14 in the breeding method of Example 2, and then 0.5 g / kg of glucose solution was administered intraperitoneally, followed by tails at 0, 30, 90, and 120 minutes, respectively. Blood glucose was measured by intravenous blood collection. Blood Glucose Measurement The blood glucose concentration of each time period was represented based on the blood glucose concentration of 100 minutes.
  • HOMA-IR insulin resistance
  • lipid was extracted from the extracted liver and dried, and the dried lipid residue was dissolved in 1 ml of ethanol.
  • Triton X-100 and sodium cholate solution in distilled water were added to emulsify.
  • the total cholesterol and triglyceride contents of liver were measured using Asan enzymatic kits (Asan, Seoul, South Korea), and the free fatty acid content was measured using Wako NEFA kit (Wako Pure Chemical Industries, Osaka, Japan).
  • the chrysanthemum leaf alcohol extract (CLE1) according to the present invention was prepared, and the chrysanthemum flower hot water extract (CLE2) and chrysanthemum methanol extract (CLE3) were prepared by the previously studied method. More specifically, in the case of chrysanthemum flower hot water extract (CLE2), 2 kg of chrysanthemum flower was extracted by hot water at 90 ° C. for 15 minutes, and the chrysanthemum methanol extract was extracted by adding 99.9% methanol (methanol), an extraction solvent, to 48 kg of chrysanthemum outpost for 48 hours at room temperature. It was. The two extracts were concentrated and freeze dried.
  • methanol methanol
  • the cats were categorized into 10 groups of + 1.5% chrysanthemum flower hot water extract) and chrysanthemum methanol extract feeding group (CLE3, high-fat diet + 1.5% chrysanthemum methanol extract) for 12 weeks and fed fasting blood sugar at 4 week intervals. Measured.
  • high-fat diet group significantly increased fasting blood sugar at 4 weeks of breeding compared to the normal diet group (ND), and extracted with chrysanthemum leaf alcohol extract (CLE1) Chrysanthemum flower hot water extract (CLE2) significantly reduced fasting blood glucose compared to the high fat diet group (HFD).
  • chrysanthemum leaf alcohol extract group (CLE1) of the present invention showed a statistically more significant effect of inhibiting blood glucose increase than the chrysanthemum flower hydrothermal extract group (CLE2).
  • Chrysanthemum leaf alcohol extract (CLE1) according to the present invention in weeks 8 and 12 was found to have an excellent hypoglycemic effect compared to the chrysanthemum flower hot water extract (CLE2) and chrysanthemum methanol extract (CLE3).
  • Plasma glucose, insulin content and HOMA-IR values were measured and analyzed for the mice of each group bred for 12 weeks by the method of Example 5.
  • the high-fat diet group (HFD) significantly increased plasma glucose, insulin and HOMA-IR levels compared to the normal diet group (ND).
  • the chrysanthemum leaf alcohol extract group (CLE1) and the previously studied chrysanthemum flower hot water extract group (CLE2) were significantly reduced than the high-fat diet group (HFD), but the chrysanthemum methanol extract group (CLE3) was There was no significant difference.
  • Plasma insulin and HOMA-IR an insulin resistance marker, were significantly lower than the high fat diet (HFD) group, but the chrysanthemum leaf alcohol extract group (CLE1) showed the best plasma insulin and HOMA-IR levels. Reduced.
  • the chrysanthemum leaf alcohol extract (CLE1) according to the present invention compared to the chrysanthemum flower hot water extract (CLE2) and chrysanthemum methanol extract (CLE3), as well as fasting blood sugar, excellent insulin resistance by reducing the overall antidiabetic The effect was confirmed to be excellent.
  • the capsule was prepared by filling in gelatin capsules according to the conventional method for producing a capsule.
  • Injectables were prepared by mixing the above ingredients per ampoule (2 ml) according to the usual method for preparing injectables.
  • Chrysanthemum leaf extract 20-95% by weight was prepared for health promotion cooking seasoning.
  • chrysanthemum leaf extract 0.2-1.0% by weight of chrysanthemum leaf extract was added to tomato ketchup or sauce to prepare tomato ketchup or sauce for health promotion.
  • Chrysanthemum leaf extract 0.5-5.0% by weight was added to the flour, using this mixture to prepare bread, cakes, cookies, crackers and noodles to produce health foods.
  • Chrysanthemum leaf extract 0.1-5.0% by weight was added to soups and gravy to prepare health-promoting meat products, noodle soup and gravy.
  • chrysanthemum leaf extract 5-10% by weight was added to milk and various milk products, such as butter and ice cream, were prepared using the milk.
  • Chrysanthemum leaf extract (2.5% solids, 97.16%), jujube extract (65 brix, 2.67%), overweight extract (solids 70%, 0.12%), vitamin C (0.02%), calcium pantonthenate (0.02%), licorice
  • a homogeneous blend of extracts (65% solids, 0.01% solids) was instantaneously sterilized and then packaged in small packaging containers such as glass bottles and plastic bottles to prepare healthy drinks.
  • chrysanthemum leaf extract was added to 1,000 ml of apple or grape juice to prepare fruit juice for health promotion.
  • a health functional food was prepared according to a conventional method.
  • the pharmaceutical composition for preventing or treating diabetes mellitus comprises chrysanthemum leaf extract as an active ingredient, when the chrysanthemum leaf extract is administered to a dietary obesity-induced mouse model, the fasting blood sugar is lowered, and plasma glucose and plasma insulin are reduced. It was confirmed experimentally that the effect of improving insulin resistance, such as lowering and inhibiting the increase of C-peptide content. Accordingly, the chrysanthemum leaf extract is expected to be useful for improving blood sugar and preventing and treating insulin resistance-related diseases, and for preventing or improving insulin resistance-related diseases, which are characterized by controlling blood sugar and insulin secretion. It can also be used as a health functional food composition.

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  • Health & Medical Sciences (AREA)
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  • Coloring Foods And Improving Nutritive Qualities (AREA)
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Abstract

La présente invention concerne une composition pharmaceutique destinée au traitement prophylactique ou thérapeutique du diabète comprenant un extrait de feuille de chrysanthème en tant que principe actif, et une composition alimentaire fonctionnelle pour la santé destinée à la prévention ou l'amélioration du diabète. Il a été spécifiquement confirmé que l'extrait de feuille de chrysanthème selon la présente invention diminue le glucose sanguin à jeun, le glucose plasmatique et l'insuline plasmatique, et améliore la résistance à l'insuline, par exemple en inhibant une augmentation de la teneur en peptide C, etc. dans un modèle animal de l'obésité induite par le régime alimentaire. Par conséquent, l'extrait de feuille de chrysanthème peut être utilisé efficacement pour améliorer le glucose sanguin et prévenir, améliorer et traiter des maladies liées à la résistance à l'insuline.
PCT/KR2018/003191 2017-03-20 2018-03-19 Composition pharmaceutique pour le traitement prophylactique ou thérapeutique du diabète comprenant un extrait de feuille de chrysanthème en tant que principe actif Ceased WO2018174502A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR10-2017-0034799 2017-03-20
KR10-2017-0139264 2017-03-20
KR1020170034799 2017-03-20
KR1020170139264A KR20180106823A (ko) 2017-10-25 2017-10-25 국화잎 추출물을 유효성분으로 포함하는 당뇨병 예방 또는 치료용 약학적 조성물

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WO2018174502A1 true WO2018174502A1 (fr) 2018-09-27

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12128082B2 (en) 2021-12-23 2024-10-29 Industrial Technology Research Institute Method for extracting flavone aglycones in chrysanthemum morifolium, extract obtained thereby and anti-inflammatory pharmaceutical composition

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0873369A (ja) * 1994-09-01 1996-03-19 Fuairudo:Kk 健康茶
CN101648024A (zh) * 2009-09-02 2010-02-17 吴光彦 用于ogtt的葡萄糖液体药用制品及制备方法
CN105456704A (zh) * 2015-12-16 2016-04-06 济南舜祥医药科技有限公司 一种用于治疗糖尿病的中药组合物

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0873369A (ja) * 1994-09-01 1996-03-19 Fuairudo:Kk 健康茶
CN101648024A (zh) * 2009-09-02 2010-02-17 吴光彦 用于ogtt的葡萄糖液体药用制品及制备方法
CN105456704A (zh) * 2015-12-16 2016-04-06 济南舜祥医药科技有限公司 一种用于治疗糖尿病的中药组合物

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
YAMAMOTO, JUNPEI ET AL.: "Hot Water Extracts of Edible Chrysanthemum Morifolium Ramat. Exert Antidiabetic Effects in Obese Diabetic KK-Ay Mice", BIOSCIENCE, BIOTECHNOLOGY, AND BIOCHEMISTRY, vol. 79, no. 7, 10 February 2015 (2015-02-10), pages 1147 - 1154, XP055559342 *
YANG, JINFENG ET AL.: "Determination of Antioxidant and alpha-glucosidase Inhibitory Activities and Luteolin Contents of Chrysanthemum Morifolium Ramat Extracts", AFRICAN JOURNAL OF BIOTECHNOLOGY, vol. 10, no. 82, 19 December 2011 (2011-12-19), pages 19197 - 19202, XP055559347 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12128082B2 (en) 2021-12-23 2024-10-29 Industrial Technology Research Institute Method for extracting flavone aglycones in chrysanthemum morifolium, extract obtained thereby and anti-inflammatory pharmaceutical composition

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