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WO2014069691A1 - Composition pour traiter le cancer rénal et aliment santé fonctionnel contenant un extrait de cnidium monnieri - Google Patents

Composition pour traiter le cancer rénal et aliment santé fonctionnel contenant un extrait de cnidium monnieri Download PDF

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Publication number
WO2014069691A1
WO2014069691A1 PCT/KR2012/009064 KR2012009064W WO2014069691A1 WO 2014069691 A1 WO2014069691 A1 WO 2014069691A1 KR 2012009064 W KR2012009064 W KR 2012009064W WO 2014069691 A1 WO2014069691 A1 WO 2014069691A1
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Prior art keywords
composition
kidney cancer
extract
present
casualty
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Ceased
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PCT/KR2012/009064
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English (en)
Korean (ko)
Inventor
황성연
정경채
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GYEONGSANGBUK-DO MEDICAL CROP CLUSTER
KOREA BIO MEDICAL SCIENCE INSTITUTE Co Ltd
Original Assignee
GYEONGSANGBUK-DO MEDICAL CROP CLUSTER
KOREA BIO MEDICAL SCIENCE INSTITUTE Co Ltd
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Priority to PCT/KR2012/009064 priority Critical patent/WO2014069691A1/fr
Publication of WO2014069691A1 publication Critical patent/WO2014069691A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/234—Cnidium (snowparsley)
    • 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 filamentous extract. Specifically, the present invention relates to a therapeutic composition and functional food containing a casualty extract showing an effective prophylactic or therapeutic effect against kidney cancer as an active ingredient.
  • the kidney is an important urinary system that has the role of excreting waste products in vitro by filtering blood to produce urine. At the same time, it is also an important endocrine organ that produces hormones such as angiotensin, which regulates blood pressure, and erythropoietin, a red blood cell hematopoietic factor. Renal tumors include kidney cell cancer in adults, Wilms' tumor in children, and sarcoma as a rare tumor, but the most common malignancy below Renal cell cancer, a tumor, is called kidney cancer. The incidence of renal cancer is about 2.5 per 100,000 population, and male to female ratio is 2 to 3: 1. Among urological malignancies, there are many tumors following prostate cancer and bladder cancer.
  • kidney cancer Genetic factors are also known as risk factors for kidney cancer, but generally include smoking and excessive fat intake. It is also known that the incidence of such tumors is high in patients undergoing long-term dialysis. In kidney cancer, when the tumor has a maximum diameter of 5 cm or less, some subjective symptoms rarely occur and are often found by CT scan or the like at the time of examination. Larger tumors may include hematuria, abdominal tumors, and pain. In addition, systemic symptoms may cause fever, weight loss, anemia and the like, and rarely, endocrine factors may cause erythrocytosis, hypertension, hypercalcemia, and the like.
  • vein veins of the abdominal body surface or venous varicose veins occur due to the progression of kidney cancer into the inferior vena cava.
  • About 20% of kidney cancers are found from lung or bone metastases.
  • tumors tend to spread in veins, and metastasis to other organs is likely to occur.
  • VHL von-Hippel-Lindau
  • the main treatment for kidney cancer is surgical therapy. Regardless of the timing of the disease, extraction of the kidneys or partial extraction of the kidneys is the most common where possible, and even if there is metastasis, surgical removal of the kidneys may be considered.
  • Arterial embolization of the renal artery may be used as a method other than the surgical therapy. This method may be performed prior to surgery in cases where it is impossible to extract or when a large tumor is removed.
  • Recent advances in burn diagnostics have led to early detection of renal cancer, even at very small sizes, resulting in more than 90% healing in early cancer. However, since the therapeutic results of large tumors larger than 5 cm or tumors with metastases are poor (the 5-year survival rate of all renal cell carcinomas is about 50 to 60%), the importance of early detection is recognized.
  • Torilidis Fructus refers to the dried fruit of the Torllis japonica Decandolle and the Cnidium monnieri (L.) Cussion, a plant belonging to the mountain family, and the casualty of natural, hybrid or mutant It includes everything.
  • Casualties are perennial herbaceous plants, 30-70 cm high. Young shoots are eaten as herbs, and fruits are used as astringents, anti-inflammatory agents, and insecticides.
  • the leaves are like palaces, flowers are white, like eggs, and they come from yellow, light and light, dry land. In May, the leaves are picked and dried in the shade. Casualties warm and heighten the kidneys and apply them to conditions such as male immoralism and female infertility.
  • casualties have been used for the treatment of various skin diseases such as itching, skin wounds, eczema, and swelling, and have been used as herbal medicines for being effective in gynecological diseases such as trichomoniasis. Recently, it is used not only as a herbal medicine for skin diseases but also as an insecticide ingredient.
  • the main components of the casualties are l-camphene, bergapten, beta-eudesmol, columbianetin, archanlicin and edultin. ), Isopimpinelline, and antosol (anthotoxol), and contains essential oils of about 1.3%.
  • the present inventors completed the present invention by confirming that the casualty extract can effectively kill kidney cancer cells while studying the herbal medicine for the casualty.
  • the present invention provides a composition for preventing and treating renal cancer comprising an active ingredient extracted from a casualty with an organic solvent. It is preferable that the said organic solvent is ethanol.
  • the present invention provides a functional food for preventing kidney cancer containing a casualty ethanol extract containing a food supplement acceptable food supplement as an active ingredient.
  • the present invention provides a composition for the prevention and treatment of kidney cancer, which contains a casualty ethanol extract as an active ingredient.
  • the composition of the present invention comprises a filamentous extract as an active ingredient and may additionally include a pharmaceutically acceptable carrier or diluent.
  • the ethanol extract is preferably extracted at 50 ° C. for 24 hours, wherein the ethanol extract is more preferably dried and concentrated at 45 ° C. under reduced pressure, and the ethanol Is most preferably 95%.
  • the kidney cancer is preferably renal cell cancer.
  • the filamentous extract of the present invention is possible at any site of the filament, but is preferably extracted from the fruit.
  • the extraction solution may be obtained by extraction with water or an organic solvent, and examples of the organic solvent may include lower alcohols, acetone, chloroform, methylene chloride, ether, ethyl acetate, and hexane.
  • Lower alcohols include methanol, ethanol, propanol and butanol, with ethanol being most preferred.
  • ethanol extract 1 to 5 times, preferably 3 times, 95% ethanol is added to the casualty dry matter or powder, and 10 to 100 hours, preferably 15 to 15, at a temperature of 20 to 100 ° C, preferably 40 to 60 ° C. Extraction for 40 hours, more preferably 24 hours, followed by filtration can produce an ethanol extract of casualties.
  • the filtrate obtained by filtering the extract may be concentrated under reduced pressure.
  • the extraction process may be repeated two or more times as necessary, and the extract obtained after filtration may be lyophilized or dried under reduced pressure to obtain a powder form.
  • 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.
  • the composition for treating kidney 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 medicating the filamentous extract of the present invention can be administered orally during clinical administration and can be used in the form of general pharmaceutical formulations, and 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 injectable water. 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 casualties killed ACHN kidney cancer cells at 100 ⁇ g / ml at 80.0%, and the IC 50 (half maximal inhibitory concentration) was 74.1 ⁇ g / ml.
  • the above results demonstrate that the filamentous extract of the present invention has excellent killing activity of ACHN kidney cancer cells, and further has renal cancer treatment and prophylactic activity.
  • prevention means any action that inhibits or delays the development of kidney cancer by administration of the composition.
  • treatment means any action that improves or advantageously changes the symptoms of kidney cancer by administration of the composition.
  • the filamentous extract may be extracted by using water, an organic solvent, or a mixed solvent thereof.
  • 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 kidney 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 kidney cancer used alone or used in the past.
  • the term "patient” refers to humans, horses, sheep, pigs, goats, and camels having a disease caused by kidney cancer and its direct and indirect causes, and whose symptoms may be improved by administering the composition of the present invention. Means animals such as nutrition, dogs.
  • a composition comprising the filamentous extract of the present invention, the above-mentioned kidney cancer can be effectively prevented and treated.
  • the composition of the present invention can be administered in parallel with existing kidney cancer treatments.
  • 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 gender, age, casualty status, 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 kidney cancer containing a casualty 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 present invention As a result of injecting the filamentous extract of the present invention into ACHN kidney cancer cells, it was confirmed that ACHN kidney cancer cells are killed (see FIG. 1 ). Thus, it can be seen that the casualty extract has a renal cancer therapeutic effect. Thus, in the present invention, the present invention was completed by preparing a functional food for preventing kidney cancer containing a casualty extract (see Preparation Example 2 ).
  • the filamentous extract of the present invention inhibits the growth of kidney cancer cells and induces apoptosis. Therefore, the composition for treating renal cancer according to the present invention will be very effective in the treatment of renal cancer patients.
  • ACHN cells which are human kidney cancer cells
  • 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.
  • ACHN cells a kidney cancer cell line used in the present invention, were distributed from Korean Cell Line Bank (KCLB) and used for experiments. Specifically, ACHN kidney cancer cells (Minimum essential medium) containing 10% FBS (fetal bovine serum, fetal bovine serum) (Welgene) and 25 mM HEPES (4- (2-hydroxyethyl) -1-piperazineethanesulfonic acid) Subcultured in medium.
  • FBS fetal bovine serum, fetal bovine serum
  • HEPES 4- (2-hydroxyethyl) -1-piperazineethanesulfonic acid
  • the filamentous extract extracted in Example 1 confirmed the effect of inhibiting growth against ACHN cells which are kidney cancer cells. Specifically, 6.0 x 10 per well in a 96 well plate 3 Seeds dissolved in dimethyl sulfoxide (DMSO) after seeding ACHN kidney cancer cells and incubating for 24 hours 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 and FIG. 1).
  • DMSO dimethyl sulfoxide
  • Acute toxicity test was performed using 6-week-old SPF SD rats. Two animals per group were suspended orally administered at a dose of 5 g / kg, each of the filamentous extract of Example 1 of the present invention suspended in 0.5% methylcellulose solution. After administration of the test substance, mortality, clinical symptoms, and changes in body weight were observed. Hematological and hematological examinations were performed. Necropsy was performed to observe abdominal and thoracic organ abnormalities.
  • the present inventors have confirmed that the renal cancer treatment effect of the casualty extract through the above example was prepared to prepare a renal cancer therapeutic agent containing the casualty extract as an active ingredient as follows.
  • the preparation of the following therapeutic agents can be used for the application of not only therapeutic agents but also casual foods.
  • the inventors have confirmed that the filamentous extract has excellent renal cancer therapeutic activity through the above-described examples, and prepared functional foods containing the same as an active ingredient as follows.
  • Chewing gum was prepared using a conventional method using the composition and content of 20% of gum base, 76.36 to 76.76% of sugar, 0.24 to 0.64% of filamentous extract, 1% of fruit flavor, and 2% of water.
  • Candy was prepared by the conventional method using the composition and content of 50-60% of sugar, 39.26-49.66% of starch syrup, 0.24-0.64% of filamentous extract, and 0.1% of orange flavor.

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Abstract

La présente invention concerne une nouvelle utilisation d'un extrait de Cnidium monnieri, et plus particulièrement une composition et un aliment santé fonctionnel contenant comme ingrédient actif un extrait de Cnidium monnieri présentant un effet important de prévention ou de traitement du cancer rénal. L'extrait de Cnidium monnieri selon la présente invention inhibe efficacement la croissance des cellules de cancer rénal et induit l'apoptose, et peut donc être efficacement utilisé dans le traitement et la prévention du cancer rénal.
PCT/KR2012/009064 2012-10-31 2012-10-31 Composition pour traiter le cancer rénal et aliment santé fonctionnel contenant un extrait de cnidium monnieri Ceased WO2014069691A1 (fr)

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KR100439209B1 (ko) * 2001-03-30 2004-07-07 남종현 스테미너 증진용 천연차 및 그 제조방법
KR20100102756A (ko) * 2009-03-12 2010-09-27 원광대학교산학협력단 사상자추출물을 함유하는 면역증강용 조성물
KR101119647B1 (ko) * 2011-04-11 2012-03-13 한국폴리텍바이오대학산학협력단 사상자 추출물을 유효성분으로 포함하는 염증성 질환 치료 및 예방용 조성물
KR20120084121A (ko) * 2011-01-19 2012-07-27 주식회사한국전통의학연구소 사상자 추출물을 포함하는 뇌암 치료용 조성물 및 건강 기능성 식품
KR20120111113A (ko) * 2011-03-31 2012-10-10 주식회사한국전통의학연구소 건강 추출물을 포함하는 신장암 치료용 조성물 및 건강 기능성 식품

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KR100439209B1 (ko) * 2001-03-30 2004-07-07 남종현 스테미너 증진용 천연차 및 그 제조방법
KR20100102756A (ko) * 2009-03-12 2010-09-27 원광대학교산학협력단 사상자추출물을 함유하는 면역증강용 조성물
KR20120084121A (ko) * 2011-01-19 2012-07-27 주식회사한국전통의학연구소 사상자 추출물을 포함하는 뇌암 치료용 조성물 및 건강 기능성 식품
KR20120111113A (ko) * 2011-03-31 2012-10-10 주식회사한국전통의학연구소 건강 추출물을 포함하는 신장암 치료용 조성물 및 건강 기능성 식품
KR101119647B1 (ko) * 2011-04-11 2012-03-13 한국폴리텍바이오대학산학협력단 사상자 추출물을 유효성분으로 포함하는 염증성 질환 치료 및 예방용 조성물

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Title
KIM, HWAN SU ET AL.: "Hemostatic Action of Torilis fructus", THE PHARMACEUTICAL SOCIETY OF KOREA, vol. 39, no. 1, February 1995 (1995-02-01), pages 55 - 60, XP053002292 *

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