WO2012134164A2 - Composition pour le traitement du cancer du poumon et aliment fonctionnel contenant un extrait de flos farfarae - Google Patents

Composition pour le traitement du cancer du poumon et aliment fonctionnel contenant un extrait de flos farfarae Download PDF

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Publication number
WO2012134164A2
WO2012134164A2 PCT/KR2012/002272 KR2012002272W WO2012134164A2 WO 2012134164 A2 WO2012134164 A2 WO 2012134164A2 KR 2012002272 W KR2012002272 W KR 2012002272W WO 2012134164 A2 WO2012134164 A2 WO 2012134164A2
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Prior art keywords
lung cancer
composition
extract
present
active ingredient
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English (en)
Korean (ko)
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WO2012134164A3 (fr
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황성연
정경채
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Korea Bio Medical Science Institute Co Ltd
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Korea Bio Medical Science Institute Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to a novel use of the Kanto extract.
  • the present invention relates to a therapeutic composition and functional food containing a Kanto extract, which shows excellent preventive or therapeutic efficacy against lung cancer, as an active ingredient.
  • Lung cancer refers to malignant tumors in the lungs, and it can be divided into primary lung cancers in which tissues of the lungs, such as bronchus, bronchioles, alveoli, etc. have.
  • Non-small cell lung cancer which accounts for 80% to 85% of all lung cancers, can be treated by surgical treatment if diagnosed early. Due to the nature of difficult lung cancer, it is often found late and difficult to treat.
  • Non-small cell lung cancer consists of three subtypes: 40% adenocarcinoma, 40% squamous cell carcinoma and 20% large cell carcinoma.
  • TMN staging system is widely accepted for the management of lung cancer.
  • T1-T4 Primary tumors are divided into four T categories (T1-T4) according to tumor size, site and local involvement. Lymph node spread is delivered into the bronchus / pulmonary in the lung (N1), medial spread on the same side as the primary tumor (N2) and mediastinal spread across the primary lung tumor. Or supraclavilcular involvement (N3). There is no distant or metastatic spread (M0 or M1). In general, lung cancer that has not metastasized is treated by surgical removal. However, recurrence rates after lung cancer removal surgery are high (20-50%) (Cancer: Principles & Practice of Oncology, 56th. Ed. In: Devita DV, Hellman S, Rosenberg SA, eds. Philadelphia, PA: Lippincott Williams & Wilkins, 2001 ).
  • non-small cell lung cancer has a high recurrence rate after treatment, and compared with a high incidence rate, resistance to conventional chemotherapy with an anticancer agent is easily generated, making it difficult to treat effectively.
  • the 10-year survival rate is very low, less than 10% despite the recent development of cancer therapy. Therefore, it is very important to develop a treatment for such non-small cell lung cancer.
  • Farfarae Flos Tussilago farfara
  • Tussilago farfara is a perennial herb belonging to the chrysanthemum family.
  • buds are called Kanto flowers. It is known to be used when there is sea water and asthma due to boiling and sometimes bloody symptoms or colds. Its ingredients are known to contain sterols, fullavonoids, and tannin compounds (Kim Chang-min et al., Medicinal Metabolism Vol. 1, p439 ⁇ 44, Jungdam, 1997). Kanto is spicy and the nature is hot ( In oriental medicine, there is a lubricity, which is characterized by darkening and expectoration.
  • the drug should be shaped like a brush and the base should be gray or turquoise with a short peduncle.
  • Kwan-dong paintings are Kanto, Tho-dong, Kanto, Gong-dong, Donghae, Fairy Tales, Jeo-dong, Chan-dong, and Tong-oh. ), Also called a lake.
  • Kwandonghwa according to the herbaceous wood, is used to steam the sea, heat insulation, and cook Korean waste. The flower decoction has been reported to act as expectorant, cough-up, and polysaccharides contained in the Kantoan anti-inflammatory activity in experimental animals.
  • Cough sputum medicine, anti-inflammatory is used for bronchial asthma, laryngitis, bronchiectasis, pneumonia, bronchitis, gastrointestinal catarrh, inflammation of the kidneys and urethra, fever.
  • the present inventors completed the present invention by confirming that the Kanto extract extract can effectively kill lung cancer cells while studying herbal medicine for Kanto.
  • the present invention provides a composition for preventing and treating lung cancer, comprising an active ingredient extracted from Kanto ( Farfarae Flos ) with an organic solvent.
  • the organic solvent is preferably ethanol.
  • the present invention provides a functional food for preventing lung cancer containing a Farfarae Flos ethanol extract containing a food supplement acceptable food supplement as an active ingredient.
  • the present invention provides a composition for preventing and treating lung cancer containing Farfarae Flos ethanol extract as an active ingredient.
  • the composition of the present invention comprises a Kantoin extract as an active ingredient, and may further include a pharmaceutically acceptable carrier or diluent.
  • the ethanol extract is preferably extracted for 24 hours at 50 °C, wherein the ethanol extract is more preferably dried and concentrated under 45 °C reduced pressure conditions, the ethanol is Most preferred is 95%.
  • the lung cancer is preferably non-small cell lung cancer, wherein the non-small cell lung cancer is adenocarcinoma (adenocarcinoma), squamous cell carcinoma (squamous cell carcinoma) and large cell cancer ( More preferably caused by a carcinoma selected from the crowd consisting of large cell carcinoma.
  • adenocarcinoma adenocarcinoma
  • squamous cell carcinoma squamous cell carcinoma
  • large cell cancer More preferably caused by a carcinoma selected from the crowd consisting of large cell carcinoma.
  • lung cancer refers to a malignant tumor occurring in the lung, and includes both small cell lung cancer and non-small cell lung cancer such as adenocarcinoma, squamous cell carcinoma, and large cell lung cancer.
  • the "pharmaceutically acceptable carrier” is a pharmaceutically acceptable substance such as a liquid or solid filler, diluent, excipient or solvent which serves to transport the active ingredient from one organ or part of the body to another organ or part of the body. , Composition or vehicle.
  • composition for treating lung cancer of the present invention may be prepared as a medicament by adding one or more pharmaceutically acceptable carriers together with the active ingredient.
  • the carrier may include, but is not limited to, saline, buffered saline, water, glycerol and ethanol, and any suitable agent known in the art (Remingtons's Pharmaceutical Science (Recent Edition), Mack Publishing Company, Easton PA) may be used. .
  • Formulations for pharmaceutical formulation of the Kantoin extract of the present invention can be administered orally at the time of clinical administration and can be used in the form of general pharmaceutical formulations, when formulated, commonly used fillers, extenders, binders, wetting agents, disintegrants, It is prepared using diluents or excipients such as surfactants.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc.
  • liquid preparations for oral use include suspensions, solvents, emulsions, and syrups.
  • various excipients may be included, such as wetting sweeteners, fragrances, preservatives and the like.
  • the herbal medicine that may be added to the composition of the present invention may be any pharmaceutically acceptable herbal medicine, for example, Angelica tenuissimae Radix, Gastrodiae Rhizoma, Bapleuri Radix, Angelica ( Angelicae gigantis Radix, Persicae Semen, Cinnamomi Ramulus, Rhubarb (Rhei Rhizoma), Licorice (Glycyrrhizae Radix), Cnidii Rhizoma, Aurantii nobilis Pericarpium, Taxa (Alismatis Rhizoma) Coptidis Rhizoma, Scutellariae Radix, Hoelen, Peeoniae Radix, Atractylodis Rhizoma alba, Phellodendri Cortex, Gardeniae Fructus, Pinelliae Tuber, Ramulu Set (Uncaria) Uncus, Ponciri Fructus, Ginseng, Gingseng, Liriopis Tuber, Poly
  • composition of the present invention may be administered in various parenteral formulations during actual clinical administration, and solid preparations include tablets, pills, powders, granules, capsules, and the like.
  • solid preparations include tablets, pills, powders, granules, capsules, and the like.
  • excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included.
  • preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories.
  • non-aqueous solvent and the suspension solvent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used.
  • base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
  • calcium or vitamin D 3 may be added to enhance the efficacy of the treatment.
  • Such compositions may be presented in unit-dose (single) or multi-dose (several) containers, such as sealed ampoules and vials, and immediately before use, sterile liquid carriers such as water for injection Can be stored under freeze-drying conditions requiring only the addition of. Immediate injection solutions and suspensions can be prepared from sterile powders, granules and tablets.
  • the formulations of the present invention can be applied differently depending on the age, sex, condition of the subject, the absorption of the active ingredient in the body, the inactivation rate and excretion rate, the drug used in combination.
  • the invention also includes formulations of dosage units.
  • the formulations are present in individual dosage forms, such as tablets, coated tablets, capsules, pills, suppositories, and ampoules, wherein the amount of active compound in the drug corresponds to the fraction or multiple of the individual dosage.
  • Dosage units may contain, for example, one, two, three or four times the individual dosage, or 1/2, 1/3 or 1/4 times.
  • the individual dosages preferably contain an amount in which the active compound is administered at one time, which usually corresponds to all, 1/2, 1/3 or 1/4 times the daily dosage.
  • extract refers to an active ingredient isolated from natural products.
  • the extract may be obtained by an extraction process using water, an organic solvent, or a mixed solvent thereof, and includes an extract, a dry powder thereof, or any form formulated using the same.
  • the ethanol extract of Kantoin kills 995% of A549 non-small cell lung cancer cells at 100 ⁇ g / ml and the EC 50 (half maximal effective concentration) was 48.5 ⁇ g / ml.
  • the above results demonstrate that the Kantoin extract of the present invention has excellent killing activity of A549 non-small cell lung cancer cells and further has lung cancer treatment and prophylactic activity.
  • prevention means any action that inhibits or delays the development of lung cancer by administration of the composition.
  • treatment means any action that improves or advantageously changes the symptoms of lung cancer by administration of the composition.
  • the Kantoin extract may be extracted by using water, an organic solvent, or a mixed solvent thereof.
  • it is extracted using an organic solvent, in particular ethanol.
  • the extracted solution can be used directly or can be concentrated and / or dried.
  • methanol, ethanol, isopropanol, butanol, ethylene, acetone, hexane, ether, chloroform, ethyl acetate, butyl acetate, dichloromethane, N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), 1,3-butylene glycol, propylene glycol, or a mixed solvent thereof may be used and extracted by room temperature or warming under conditions where the active ingredient of the herbal medicine is not destroyed or minimized.
  • the degree of extraction and loss of the active ingredient of the drug may vary, so select an appropriate organic solvent.
  • the extraction method is not particularly limited, and examples thereof include cold needle extraction, ultrasonic extraction, reflux cooling extraction, and the like.
  • Filtration is a process of removing the suspended solid particles from the extract, it may be used to filter the particles using cotton, nylon or the like, or may be used, such as ultrafiltration, cryofiltration, centrifugal separation, but is not limited thereto.
  • Concentration of the extract may be used, such as concentrated under reduced pressure, reverse osmosis concentration.
  • the drying step after concentration includes freeze drying, vacuum drying, hot air drying, spray drying, reduced pressure drying, foam drying, high frequency drying, infrared drying, and the like. If desired, a process of grinding the final dried extract may be added.
  • the extract can perform an additional fractionation process.
  • the extract is suspended in distilled water to obtain a nonpolar solvent soluble layer by extraction and separation with a nonpolar organic solvent such as hexane, ether, dichloromethane, chloroform, ethyl acetate, or a mixed solvent thereof. It can be used by concentrating and / or drying it.
  • a nonpolar organic solvent such as hexane, ether, dichloromethane, chloroform, ethyl acetate, or a mixed solvent thereof. It can be used by concentrating and / or drying it.
  • the term "pharmaceutically acceptable salts” means salts derived from pharmacologically or physiologically acceptable inorganic acids, organic acids and bases.
  • suitable acid include hydrochloric acid, bromic acid, sulfuric acid, nitric acid, perchloric acid, fumaric acid, maleic acid, phosphoric acid, glycolic acid, lactic acid, salicylic acid, succinic acid, toluene-p-sulfonic acid, tartaric acid, acetic acid, citric acid, methanesulfonic acid, Formic acid, benzoic acid, malonic acid, naphthalene-2-sulfonic acid, benzenesulfonic acid, and the like.
  • Salts derived from suitable bases may include alkali metals such as sodium, alkaline earth metals such as magnesium, ammonium and the like.
  • the pharmaceutical composition for preventing and treating lung cancer diseases of the present invention comprises 0.1 to 50% by weight of the extract or compound based on the total weight of the composition.
  • the composition does not increase the efficacy, but may include additional ingredients that are commonly used in the pharmaceutical composition to improve the smell, taste, time and the like.
  • the composition adds inorganic and organic additives such as vitamins B1, B2, B6, C, E, niacin, carnitine, betaine, folate pantothenic acid, biotin, zinc, iron, calcium, chromium, magnesium, and mixtures thereof. It can be included as.
  • the composition may include a substance having a therapeutic activity against lung cancer, used alone or previously used.
  • the term "patient” refers to humans and horses, sheep, pigs, goats, camels, Means antelope, dog and other animals.
  • a composition comprising the Kantoin extract of the present invention, the above-mentioned lung cancer can be effectively prevented and treated.
  • the composition of the present invention can be administered in parallel with existing lung cancer therapeutics.
  • the term "administration” means introducing a predetermined substance into a patient by any suitable method, and the route of administration of the composition of the present invention is oral or parenteral via any general route as long as the target tissue can be reached. May be administered.
  • the composition may be administered by any device in which the active agent may migrate to the target cell.
  • 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 an effective dose level refers to a patient's sexually transmitted disease, age, severity, and drug activity.
  • the compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents and may be administered sequentially or simultaneously with conventional therapeutic agents. It may be single or multiple doses.
  • the method of administering the composition comprising the extract or compound prepared according to the preparation method of the present invention is preferably oral administration or intravenous administration.
  • the effective dose is oral administration, it is usually 1 to 1 time per adult. 500 mg / kg is preferred, and in the case of intravenous administration, 1 to 100 mg / kg is preferred, and may be administered 2-3 times a day.
  • Dosage levels for a particular patient may vary depending on sex, age, health condition, diet, time of administration, method of administration, drug mixture, the condition of the patient, and the extent of the onset of neurological disease.
  • the present invention provides a functional food for preventing lung cancer containing a Farfarae Flos ethanol extract containing a food supplement acceptable food supplement as an active ingredient.
  • Functional food of the present invention preferably contains 0.1 to 5% by weight, more preferably 1% by weight of the ethanol extract relative to the total weight.
  • Functional food of the present invention is not particularly limited in the formulation, for example, dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, ice cream, Various soups, beverages, tea, drinks, alcoholic beverages and vitamin complexes, etc., and includes all of the health food in the usual sense.
  • “functional food” means a food manufactured and processed using raw materials or ingredients having functional properties useful for the human body according to Act No. 6767 of the Health Functional Food Act, and “functional” refers to the structure of the human body And ingestion for the purpose of obtaining nutrients for function or for obtaining useful effects in health uses such as physiological actions.
  • the A549 non-small cell lung cancer cells were injected with the percutaneous extract of the present invention, and A549 non-small cell lung cancer cells were confirmed to die (see FIG. 1 ). Therefore, it can be seen that the Kanto extract is effective in treating lung cancer.
  • the present invention was completed by preparing a functional food for lung cancer prevention containing the Kantoin extract as an active ingredient (see Preparation Example 2 ).
  • the Kantoin extract of the present invention inhibits the growth of lung cancer cells and induces apoptosis. Therefore, the composition for treating lung cancer according to the present invention will be very effective in the treatment of lung cancer patients.
  • A549 non-small cell lung cancer cells which are human lung cancer cells
  • the X-axis is the concentration of the tuberculosis extract
  • the Y-axis is surviving human lung cancer The viability of the cells is shown.
  • A549 non-small cell lung cancer cells which are human lung cancer cells, were treated with ethanol extract of Kanto for 48 hours and subjected to Alamar Blue analysis.
  • the Alamar Blue assay is a modified form of the MTT assay, in which a specific enzyme degrades a living cell and then measures the fluorescence intensity of the product as the compound breaks down to determine the relative number of living cells after treatment. I am an experimental method. It will be described in more detail below.
  • A549 cells, a lung cancer cell line used in the present invention were distributed from the Korean Cell Line Bank (KCLB) and used for experiments. Specifically, A549 lung cancer cells RPMI 1640 medium (Robwell Park Memorial) containing 10% FBS (fetal bovine serum, fetal bovine serum) (Welgene) and 25 mM HEPES (4- (2-hydroxyethyl) -1-piperazineethanesulfonic acid) Subculture was performed in a floating culture medium researched and developed by the Institute.
  • KCLB Korean Cell Line Bank
  • Kanto extract extracted in Example 1 was confirmed the effect of inhibiting the growth of lung cancer cells A549 non-small cell. Specifically, 1.4 X 10 per each well in a 96 well plate 3 The A549 lung cancer cells were seeded and incubated for 24 hours, followed by dissolution in dimethyl sulfoxide (DMSO). When the ethanol extract was treated at concentrations of 0 to 100 ⁇ g / ml (specifically, concentrations of 0, 3.125, 6.25, 12.5, 25, 50 and 100 ⁇ g / ml, respectively) for 48 hours, the degree of inhibition of cell growth was confirmed. (Table 1).
  • Kantoin used in the present invention was widely used as a medicinal herb, so it was judged that there would be no problem in stability.
  • Acute toxicity test was performed using 6-week-old SPF SD rats. Two animals per group were suspended orally at a dose of 5 g / kg in suspension of 0.5% methylcellulose solution of the Kantoin extract of Example 1 of the present invention. After administration of the test substance, mortality, clinical symptoms, and changes in body weight were observed. Hematological and hematological examinations were performed, and autopsy was performed to observe abdominal and thoracic organ abnormalities.
  • the present inventors have confirmed that the lung cancer treatment effect of the Kwandonghwa extract is excellent through the above embodiment to prepare a lung cancer therapeutic agent containing the Kwandonghwa extract as an active ingredient as follows.
  • the preparation of the following therapeutic agent can be used for the application of the health food as well as the therapeutic agent.
  • Kanto Extract 35% Vitamin C 10%, Vitamin D 3 0.001%, Manganese Sulfate 0.1%, Crystalline Cellulose 25.0%, Lactose 17.999%, Magnesium Stearate 2%
  • the present inventors have confirmed that the Kwandonghwa extract is excellent in lung cancer treatment activity through the above embodiment to prepare a functional food containing it as an active ingredient as follows.
  • Chewing gum was prepared using conventional methods using the composition and content of 20% of gum base, 76.36 to 76.76% of sugar, 0.24 to 0.64% of Kanto extract, 1% of fruit flavor, and 2% of water.

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Abstract

La présente invention concerne une nouvelle utilisation d'un extrait de flos farfarae, et plus particulièrement, une composition pour le traitement du cancer du poumon et un aliment fonctionnel contenant, comme ingrédient actif, un extrait de flos farfarae ayant d'excellents effets prophylactiques et thérapeutiques sur le cancer du poumon. L'extrait de rhizome de flos farfarae, selon la présente invention, élimine la prolifération des cellules cancéreuses dans le poumon et induit leur apoptose, et peut ainsi être utilisé efficacement dans la prophylaxie et le traitement du cancer du poumon.
PCT/KR2012/002272 2011-03-28 2012-03-28 Composition pour le traitement du cancer du poumon et aliment fonctionnel contenant un extrait de flos farfarae Ceased WO2012134164A2 (fr)

Applications Claiming Priority (2)

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KR10-2011-0027343 2011-03-28
KR1020110027343A KR20120111764A (ko) 2011-03-28 2011-03-28 관동화 추출물을 포함하는 폐암 치료용 조성물 및 건강 기능성 식품

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WO2012134164A2 true WO2012134164A2 (fr) 2012-10-04
WO2012134164A3 WO2012134164A3 (fr) 2013-03-07

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090004302A1 (en) * 2004-10-15 2009-01-01 Biopharmacopae Design International Inc. Methods and Therapeutic Compositions Comprising Plant Extracts for the Treatment of Cancer
US20080113042A1 (en) * 2006-09-05 2008-05-15 Chu Kee Hung Pharmaceutical composition and method for cancer treatment based on combinational use of conventional anticancer agents and geranium oil or compounds thereof

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