WO2015064899A1 - Composition contenant, comme principe actif, un extrait mélangé d'aune japonais, de sagesse-des-chirurgiens et de peucedanum praeruptorum, ou une fraction associée pour prévenir ou traiter un cancer - Google Patents

Composition contenant, comme principe actif, un extrait mélangé d'aune japonais, de sagesse-des-chirurgiens et de peucedanum praeruptorum, ou une fraction associée pour prévenir ou traiter un cancer Download PDF

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WO2015064899A1
WO2015064899A1 PCT/KR2014/007537 KR2014007537W WO2015064899A1 WO 2015064899 A1 WO2015064899 A1 WO 2015064899A1 KR 2014007537 W KR2014007537 W KR 2014007537W WO 2015064899 A1 WO2015064899 A1 WO 2015064899A1
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extract
cancer
composition
alder
fraction
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PCT/KR2014/007537
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English (en)
Korean (ko)
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김진희
박종식
방옥선
백명기
이진무
이준
이유진
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한국한의학연구원
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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)
    • 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
    • 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)
    • A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
    • 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 composition for preventing, ameliorating or treating cancer. More specifically, the present invention is a pharmaceutical composition for the prevention or treatment of cancer containing a mixed extract of alder, wormwood and baekhwajeon or fractions thereof as an active ingredient, a mixed extract of the alder, wormwood and baekhwahoe or fractions thereof A health functional food composition for preventing or improving cancer containing as an active ingredient, and a method for preventing or treating cancer using the composition.
  • Cancer is currently one of the most fatalities in the world, and the age of cancer is gradually decreasing, while the life expectancy is gradually increasing. According to 2013 statistics provided by the National Cancer Center [National Cancer Center, Cancer Facts & Figures 2013, p 18, 2013] There are 202,053 cases of cancer in Nara, with an estimated 270,000 people in 2015.
  • Platinum-based anticancer agents containing platinum are widely used as anticancer agents used in conventional anticancer treatments.
  • Representative agents of such platinum-based anticancer agents include cisplatin, carboplatin, and nedaplatin.
  • the present inventors conducted a study to invent a substance having excellent anti-cancer efficacy but does not cause side effects during chemotherapy, and thus the mixed extracts of alder, wormwood and baekhwa jeon are excellent natural anti-cancer ingredients and thus have side effects. It has been found that it does not cause, resulting in a composition for preventing, improving or treating cancer.
  • the present invention aims to prevent, ameliorate or treat cancer by using a mixed extract of alder, wormwood, and baekhwahoe or its fractions.
  • one object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of cancer, which contains a mixed extract of alder, wormwood and baekhwajeon or fractions thereof as an active ingredient.
  • Another object of the present invention to provide a health functional food composition for the prevention or improvement of cancer containing the mixed extract of the alder, wormwood and baekhwajeon or fractions thereof as an active ingredient.
  • Another object of the present invention is to provide a method for preventing or treating cancer, comprising administering the composition to a subject.
  • composition of the present invention acts to inhibit the growth and / or proliferation of cancer cells, to inhibit metastasis of cancer cells, and to inhibit neovascular formation, thereby effectively preventing, improving or treating cancer.
  • composition of the present invention by using the extract of the alder or the fraction thereof and the extract of the wormwood or the fraction thereof, the extract of the baekhwajeon or the fraction thereof, the synergy superior to the case of using each of these extract or fraction alone It can be effective in preventing, ameliorating or treating cancer effectively.
  • composition of the present invention is derived from natural products can be used safely without causing serious irritation or harmful action in addition to the anti-cancer effect. Therefore, when performing anticancer treatment using the composition of the present invention, it does not cause side effects to the subject to be treated.
  • Figure 1a shows the tumor volume increase inhibitory effect of the mixed extract of alder, wormwood and baekhwajeon of one embodiment of the present invention.
  • AJ is alder
  • DS is wormwood
  • PP is an extract of baekhwajeon
  • a mixed extract of each extract is represented by a "+" symbol. It is the same below.
  • Figure 1b shows the data measured the change in the volume of the tumor according to the administration of the mixed extract of alder, wormwood and baekhwajeon of one embodiment of the present invention.
  • Figure 1c shows the tumor weight increase inhibitory effect of the mixed extract of alder, wormwood and baekhwajeon of one embodiment of the present invention.
  • Figure 2 is a measure of the weight change of the mouse according to the administration of the mixed extract of alder, wormwood and baekhwajeon, which is an aspect of the present invention.
  • Figure 3a is a measure of the change in liver weight according to the administration of the mixed extract of alder, wormwood and baekhwajeon that is one embodiment of the present invention.
  • Figure 3b is a measure of the change in kidney weight according to the administration of the mixed extract of alder, wormwood and baekhwajeon of one embodiment of the present invention.
  • Figure 4a is a microscopic observation of the effect of inhibiting cell migration in vascular endothelial cells according to the treatment of the mixed extract of alder, wormwood and baekhwajeon of one embodiment of the present invention.
  • Figure 4b is the data measuring the effect of inhibiting the cell migration in vascular endothelial cells according to the treatment of the mixed extract of alder, wormwood and baekhwajeon of one embodiment of the present invention.
  • Figure 5a is a microscopic observation of the effect of tube formation in the vascular endothelial cells according to the treatment of the mixed extract of alder, wormwood and baekhwajeon of one embodiment of the present invention.
  • Figure 5b is the data measuring the effect of inhibiting tube formation in vascular endothelial cells according to the treatment of the mixed extract of alder, wormwood and baekhwajeon, which is an aspect of the present invention.
  • FIG. 6A is data showing efficacy assessments for the drugs in Table 4 for tissues of Patient # 102F in colorectal cancer PDTX animal model.
  • FIG. 6B is data showing efficacy assessments for the drugs in Table 4 for tissues of Patient # 115F in colorectal cancer PDTX animal model.
  • Figure 7 is a data showing the results of evaluating the cell death degree of the drug of Table 4 in colorectal cancer PDTX tissue by TUNEL analysis.
  • 9 is data showing the result of measuring PDTX tissue by Ki67 immunostaining as a proliferation marker.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of cancer, which contains a mixed extract of alder, wormwood and white pear, or a fraction thereof as an active ingredient.
  • a health functional food composition for preventing or improving cancer containing a mixed extract of Alder, wormwood, and Prunaceae as an active ingredient.
  • Alnus japonica of the present invention is a deciduous algae tree, also called glass tree ( ⁇ ⁇ ), red sheep ( ⁇ ⁇ ) or tea tree, belongs to the birch (Betulaceae), Alnus (Alnus), It is a plant native to Korea.
  • Descurainia Hospital of the present invention is a biennial herb, also called sperm, belongs to the Brassicaceae (Brassicaceae), genus (Descurainia), is a plant native to Korea.
  • Peucedanum praeruptorum Dunn of the present invention is a plant belonging to the mountain (Umbelliferae), and is a plant that is distinctly different from the horticulture ( Anthriscus sylvetris HOFFMANN) having a botanical name of the same name as a herbal, herbal medicine.
  • extract refers to extracts themselves, such as extracts obtained by extraction processing of natural products, dilutions or concentrates of extracts, dried products obtained by drying extracts, modifiers or purified products of extracts, or mixtures thereof. It includes extracts of all formulations that can be formed using extracts.
  • the method of extracting the alder, wormwood or baekhwajeon is not particularly limited and may be extracted according to a method commonly used in the art.
  • Non-limiting examples of the extraction method include hot water extraction, ultrasonic extraction, filtration, reflux extraction and the like.
  • the kind of the solvent used to extract the alder, wormwood or white pear is not particularly limited, and any solvent known in the art may be used.
  • Non-limiting examples of the extraction solvent may include water, alcohol or a mixed solvent thereof, and more preferably, C 1 to C 4 alcohols (methanol, ethanol, propanol, butanol). ) Can be used, more preferably ethanol.
  • the extract of the alder, wormwood or baekhwahoe of the present invention may be extracted from various organs of the natural, hybrid, varieties of alder, wormwood or baekhwahoe, for example, roots, ground, stems, leaves, Extraction can be made from plant tissue cultures as well as flowers, trunks of fruit and bark of fruit.
  • fraction refers to the result obtained by performing fractionation to separate a specific component or a specific group of components from a mixture comprising several different components.
  • the fractionation method for obtaining the fraction is not particularly limited, and may be performed according to a method commonly used in the art.
  • a method of obtaining a fraction from the extract by treating a predetermined solvent with an extract obtained by extracting alder, wormwood or baekhwajeon.
  • the kind of solvent used to obtain the fraction in the present invention is not particularly limited, and any solvent known in the art may be used.
  • Non-limiting examples of the fractionation solvents include polar solvents such as water and alcohols; Non-polar solvents, such as hexane (Hexane), ethyl acetate (Ethyl acetate), chloroform (Chloroform), and dichloromethane, are mentioned. These may be used alone or in combination of two or more thereof.
  • alcohols of C 1 to C 4 may be preferably used.
  • the mixed extract of the alder, wormwood and baekhwahoe of the present invention exhibits a superior synergistic effect in anticancer efficacy than the use of each extract of alder, wormwood and baekhwahoe alone.
  • the mixed extracts of alder, wormwood and baekhwajeon exhibit excellent synergistic effects in inhibiting tumor growth, inhibiting cancer cell metastasis, and inhibiting angiogenesis, when each of them is used alone. Compared to a significant superiority in the prevention, improvement or treatment of cancer.
  • the weight ratio of the extract of the alder or the fraction thereof, the extract of the wormwood or the fraction thereof, and the extract of the baekhwajeon or its fraction contained in the composition for preventing, improving or treating cancer of the present invention is not particularly limited, but is preferable. Preferably in a weight ratio of about 1: 1: 1. When contained in the above range, it is possible to effectively inhibit the growth of cancer cells and metastasis of cancer cells, there is an advantage that can effectively inhibit the neovascularization action.
  • composition for preventing, ameliorating or treating the cancer of the present invention may further include a pharmaceutically acceptable carrier, and may be formulated together with the carrier to provide food, medicine, feed additives, and drinking water additives.
  • pharmaceutically acceptable carrier means a carrier or diluent that does not interfere with the biological activity and properties of the compound to be administered without stimulating the organism.
  • the kind of the carrier usable in the present invention is not particularly limited, and any carrier can be used as long as it is a conventionally used and pharmaceutically acceptable carrier in the art.
  • Non-limiting examples of the carrier include saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol and the like. These may be used alone or in combination of two or more thereof.
  • additives such as antioxidants, buffers and / or bacteriostatic agents may be added and used, and diluents, dispersants, surfactants, binders, and / or lubricants may be added in addition to aqueous solutions, suspensions, emulsions, and the like. It may be formulated into the same injectable formulation, pills, capsules, granules or tablets and the like.
  • the mode of administration of the composition for preventing, ameliorating or treating the cancer of the present invention is not particularly limited and may be in accordance with a method commonly used in the art.
  • the composition may be administered by oral or parenteral administration.
  • composition for preventing, ameliorating or treating the cancer of the present invention may be prepared in various formulations according to the desired mode of administration.
  • formulations for oral administration include troches, lozenges, tablets, aqueous suspensions, oily suspensions, prepared powders, granules, emulsions, hard capsules, soft capsules, syrups or elixirs, and the like. Can be mentioned.
  • a dosage form for oral administration such as tablets or capsules, lactose, Saccharose, Sorbitol, Mannitol, Starch, Amylopectin ), Binders such as cellulose (Cellulose) or gelatin (Gelatin) and the like; Excipients such as dicalcium phosphate and the like; Disintegrants such as corn starch or sweet potato starch; Lubricating oils such as magnesium stearate, calcium stearate, sodium stearyl fumarate, polyethylene glycol wax, and the like.
  • the capsule formulation may further contain a liquid carrier such as fatty oil in addition to the above-mentioned materials.
  • parenteral administration of the composition of the present invention for example, intravenous administration, intraperitoneal administration, intramuscular administration, subcutaneous administration or topical administration may be used. Methods may also be used, but are not limited to these.
  • Formulations for parenteral administration include, for example, injectable forms such as subcutaneous injection, intravenous injection or intramuscular injection; Suppository injection mode; Or it may be formulated for spraying, such as aerosols to enable inhalation through the respiratory tract, but is not limited thereto.
  • injectable formulations the compositions of the present invention can be mixed in water with stabilizers or buffers to prepare solutions or suspensions and formulated for unit administration of ampoules or vials.
  • a propellant or the like may be combined with the additives to disperse the dispersed concentrate or wet powder.
  • Suitable application, spraying or dosage of the composition for the prophylaxis, amelioration or treatment of cancer of the present invention may be carried out by the method of formulating the composition, mode of administration, time of administration and / or route of administration, as well as the age of the animal to be administered, It may vary depending on factors such as weight, sex, extent of disease symptoms, food ingested, rate of excretion, etc. Those of ordinary skill in the art can readily determine and prescribe a dosage effective for the desired treatment. Can be.
  • cancer refers to a disease associated with cell death control, and refers to a disease caused by excessive proliferation of cells when the balance of normal apoptosis is broken. These abnormally over-proliferating cells can sometimes invade surrounding tissues and organs to form masses and cause destruction or deformation of normal structures in the body, commonly referred to as cancer.
  • tumor refers to a mass grown abnormally by autonomous overgrowth of body tissues, and the tumor may be classified into a benign tumor and a malignant tumor. Malignant tumors grow much faster than benign tumors and invade surrounding tissues, resulting in metastasis, which is life threatening. Such malignant tumors are commonly referred to as 'cancer'.
  • the type of the cancer is not particularly limited.
  • the cancer include cerebral spinal cord tumor, head and neck cancer, lung cancer, breast cancer, thymoma, mesothelioma, esophageal cancer, cancer, colon cancer, liver cancer, gastric cancer, pancreatic cancer, biliary tract cancer, kidney cancer, bladder cancer, prostate cancer, testicular cancer, germ cell tumor , Ovarian cancer, cervical cancer, endometrial cancer, colon cancer, lymphoma, acute leukemia, chronic leukemia, multiple myeloma, sarcoma, malignant melanoma, and the like.
  • composition of the present invention shows effective anticancer efficacy in cancers other than the above-described types of cancers, but is particularly effective in preventing, ameliorating or treating lung cancer, colorectal cancer, gastric cancer, hematologic cancer and lymphoma.
  • prevention means any action that inhibits or delays the onset of cancer by administering to the subject a composition for preventing, ameliorating or treating the cancer of the present invention.
  • treatment refers to all the actions of administering the composition of the present invention to a susceptible subject to cancer to improve or benefit from cancer.
  • improvement means any action that at least reduces the parameters associated with the condition being treated, such as the extent of symptoms.
  • the health functional food composition of the present invention When used as a food additive, the composition may be added as it is or used with other food or food ingredients, and may be appropriately used according to a conventional method.
  • the kind of the food is not particularly limited, and includes all foods in a general sense.
  • foods that can be added to the material include meat, sausages, bread, chocolate, candy, snacks, confectionery, pizza, ramen, dairy products, including other noodles, gums, ice cream, various soups, drinks, tea , A drink, an alcoholic beverage, and a vitamin complex.
  • the health functional food composition of the present invention is a beverage composition
  • it may contain various flavors or natural carbohydrates and the like as additional ingredients, as in the usual beverage.
  • natural carbohydrates include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Natural sweeteners such as dextrin, cyclodextrin; Synthetic sweeteners such as saccharin and aspartame; and the like.
  • the proportion of the additional components added above may be appropriately determined by the choice of those skilled in the art.
  • the health functional food composition of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin , Alcohols, carbonation agents used in carbonated beverages, and the like.
  • the health functional food composition of the present invention may contain a flesh for preparing natural fruit juice, fruit drink or vegetable drink. These components can be used independently or can be used in combination of 2 or more. The proportion of such additives may also be appropriately selected by those skilled in the art.
  • a feed additive or drinking water additive for the prevention or improvement of cancer comprising the mixed extract of the alder, wormwood and baekhwajeon or its fraction as an active ingredient.
  • the feed additive or drinking water additive of the present invention may be prepared by separately preparing a composition comprising a mixed extract of the alder, wormwood and white pear or its fraction in the form of a feed additive or drinking water additive or mixing the feed or drinking water,
  • the composition comprising a mixed extract of the alder, wormwood and baekhwajeon or fractions thereof may be used in the manner of adding directly in the preparation of feed or drinking water.
  • the feed additive or drinking water additive of the present invention may be in a liquid or dry state, preferably in the form of a dry powder.
  • the drying method for preparing the feed additive or drinking water additive of the present invention in the form of a dried powder is not particularly limited, and methods commonly used in the art may be used. Non-limiting examples of the drying method include ventilation drying, natural drying, spray drying, freeze drying and the like. These may be used alone or in a manner using two or more methods together.
  • the feed additive or drinking water additive of the present invention may further include other additives as necessary.
  • the additives that can be used include binders, emulsifiers, preservatives, etc., added to prevent deterioration of feed or drinking water; Amino acids, vitamins, enzymes, probiotics, flavoring agents, nonprotein nitrogenous compounds, silicates, buffers, coloring agents, extracting agents or oligosaccharides are added to increase the usefulness of feed or drinking water.
  • it may further include a feed mixture and the like. These may be used alone or two or more kinds may be added together.
  • a feed or drinking water for the prevention or improvement of cancer comprising a mixed extract of the alder, wormwood and baekhwajeon or fractions thereof as an active ingredient.
  • the feed or drinking water may be prepared by adding the feed additive or drinking water additive of the present invention to the feed or drinking water, or by directly adding a composition including a mixed extract of the alder, wormwood and white pear or its fractions. have.
  • the type of the feed is not particularly limited in the present invention, it is possible to use a feed commonly used in the art.
  • Non-limiting examples of the feed include, but are not limited to, vegetable feeds such as cereals, fruits, food processing by-products, algae, fibres, pharmaceutical by-products, oils, starches, gourds or grain by-products; And animal feeds such as proteins, minerals, fats and oils, minerals, fats and oils, single cell proteins, zooplankton or foods. These may be used alone or in combination of two or more thereof.
  • the kind of the drinking water is not particularly limited, and drinking water commonly used in the art may be used.
  • a method for preventing or treating cancer comprising administering to a subject a composition comprising a mixed extract of Alder, wormwood, and Prunaceae as an active ingredient.
  • the term "individual" means all animals, including humans, who have or are likely to develop cancer.
  • the method for preventing or treating the present invention specifically comprises administering to a subject having or at risk of developing cancer in a pharmaceutically effective amount of a composition comprising a mixed extract or a fraction thereof of the alder, wormwood, and pear tree. Steps. Suitable daily total amounts of the composition comprising the mixed extract of alder, wormwood and white flower or fractions thereof may be appropriately determined by those skilled in the art within the scope of good medical judgment.
  • the specific pharmaceutically effective amount of the composition for a particular animal can vary depending on the type and extent of the reaction to be achieved, the age, weight, general state of health, sex or diet of the individual, as well as the time of administration, route of administration and composition of the composition. It may be determined in consideration of the secretion rate, the duration of treatment, and the like, and may vary according to various factors and similar factors well known in the medical field, including components of drug or other compositions used simultaneously or simultaneously.
  • a preferred total daily usage of the composition comprising the mixed extract of the alder, wormwood and baekhwajeon of the present invention or fractions thereof may be about 500 mg / kg / day.
  • a mouse injected with a transdermal injection of an A549 human lung cancer cell line of the logarithmic growth stage is administered with a composition comprising the mixed extract of Alder, wormwood, and Pear pear, or a fraction thereof, the size and weight of the tumor.
  • a platinum-containing platinum-based anticancer agent such as cisplatin (Cisplatin) is equivalent to a significantly meaningful result.
  • the present invention is a composition derived from natural products, which is serious in the body in addition to the anticancer efficacy, compared to the serious side effects such as weight loss and abnormal findings in organs such as liver, kidney, spleen, etc. according to chemotherapy. It can be used safely without stimulating or causing harmful action, and therefore, when performing anticancer treatment using the composition of the present invention, there is an advantage that does not cause side effects to the subject to be treated.
  • composition of the present invention can be more usefully used in individuals having a medical condition that is difficult to use anti-cancer agents causing conventional side effects, individuals of low age or high age, and individuals having a constitution sensitive to stimuli applied to the outside of the body. Can be.
  • the route of administration and mode of administration of the composition in the prophylactic or therapeutic method of the present invention is not particularly limited and may be in accordance with any route of administration and mode of administration so long as the composition comprising the composition can reach the desired site.
  • the composition may be administered through various routes, oral or parenteral, and non-limiting examples of the route of administration include oral, rectal, topical, intravenous, intraperitoneal, intramuscular, intraarterial, transdermal, nasal What is administered through intralateral or inhalation etc. are mentioned.
  • composition of the present invention may be more preferably administered orally.
  • Alnus japonica , Descurainia Sophia and Peucedanum praeruptorum in the manufacture of a pharmaceutical composition or nutraceutical composition for the prevention, improvement or treatment of cancer Dunn's mixed extract or fractions thereof.
  • CMC Carboxymethyl cellulose
  • the seeds of commercial mugwort were obtained, dried and crushed, and then extracted at room temperature using 40 L of 80% ethanol per 9 kg of mugwort seed.
  • the extraction was carried out by exchanging the solvent each time, a total of three times were repeated for 24 hours at a time.
  • the mixture was concentrated under reduced pressure to remove the oil component of the upper layer, and the extract of the lower layer was dried and homogenized to obtain an extract of mugwort.
  • the obtained extract was dissolved in 0.5% carboxymethyl cellulose aqueous solution containing 2% ethanol at a concentration of 125 mg / ml to 500 mg / ml and stored in a frozen state.
  • the roots of the baekhwahoe were obtained, and the extract of baekhwahohoe was prepared in the same manner as the extracting method of the alder.
  • Each of the alder, wormwood and baekhwahoe extract prepared by mixing the above, or the alder, wormwood and baekhwahoe may be prepared by extracting together according to any one of the above-described methods in the raw material state.
  • n-hexane n-hexane
  • n-Hexane n-hexane
  • the filtrate was concentrated under reduced pressure to obtain a hexane fraction. It was. Then, the hexane fraction was removed and ethyl acetate was added to the remaining water layer in the same amount to obtain an ethyl acetate fraction in the same manner as above.
  • the ethyl acetate fraction was removed and the same amount of butanol was added to the remaining water layer to obtain a butanol fraction in the same manner as above. Then, the butanol fraction was removed and the remaining water layer was concentrated to obtain a water fraction.
  • the obtained hexane fraction, ethyl acetate fraction, butanol fraction and water fraction were each dried under reduced pressure and stored in a frozen state.
  • the mixed extract of each alder, wormwood and baekhwajeon prepared in Preparation Example 1 was administered to the animal experimental group to determine the tumor growth inhibitory effect of these extracts.
  • mice obtained from a central experimental animal company
  • A549 human lung cancer cell line of logarithmic growth phase was suspended in serum-free RPMI medium. 5 ⁇ 10 6 cells per mouse were injected by subcutaneous injection.
  • each mouse was administered with a mixed extract of each extract prepared in Preparation Example 1 and each extract was mixed in the composition of Table 1 below.
  • each of the substances In the administration of each of the substances, the extract was administered orally once a day, and the cisplatin was administered by intraperitoneal injection once a week. After the administration, each mouse was fed with water and feed, and the tumor size and volume of each mouse were measured twice a week. The volume of the tumor was measured by measuring the long axis and short axis length (mm) of the tumor using a calipo, and then calculating the calculation by the formula of short axis 2 ⁇ long axis ⁇ 0.52.
  • Example 2 Verification of weight loss by administration of a mixed extract of alder, wormwood and white pear
  • the cisplatin administration group showed severe weight loss after about 6 weeks, and it was confirmed that the side effect was caused by the use of cisplatin, whereas the administration of the vehicle when the mixed extract of alder, cucurbita and chlorosis was administered No weight loss was observed in mice as in the control (FIG. 2).
  • Example 3 Verification of abnormal findings of organs by administration of a mixed extract of alder, wormwood and white pear
  • vascular endothelial cells 100,000 human-derived vascular endothelial cells (HUVEC) per well were cultured in 500 ml of EGM-2 medium for 24 hours in a 24 well plate, and then, using a pipette. A wound was created. Then, 20 hours after treatment with each extract while replacing the medium, the extent of damage healing was measured in% relative to vehicle.
  • the length of the tube was formed into a blood vessel shape after 8 hours of treatment with each extract. Compared with the control.
  • the alder extract As a result of the cell migration test and tube formation test, among the extracts of the mugwort, alder and algae, the alder extract was found to be particularly effective in inhibiting angiogenesis by partially inhibiting cell migration and tube formation. In the case of the mixed extract treatment of the previous issue, it was confirmed that the angiogenesis inhibitory effect is much superior to the alder extract alone treatment group (Fig. 4a, 4b, 5a, and 5b).
  • the PDTX (patient-derived tumor xenograft) model system detects the reactivity of the anticancer drugs and the efficacy of candidate drugs by transplanting and growing cancer tissues of patients acquired through surgery or biopsy into experimental animals that lack immunity. in vivo model.
  • the cancer tissue obtained from colon cancer patients in Korea was transplanted to immune-deficient Balb / c nude mice, and when the tumor grew to an average size of about 200 mm 3 , the group was randomly divided and then prepared.
  • the extract prepared in Table 1 in the composition of Table 4. As a control drug, oxaliplatin, which is widely used for treating colorectal cancer, was used.
  • the cancer tissues were recovered and measured by the TUNEL assay.
  • the apoptosis was increased in proportion to the administration concentration in the alder: wormwood: chlorophyll mixed extract administration group compared to the control group. Induction of apoptosis in the administration group was confirmed to show superior results compared to the positive control (Fig. 7).

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Abstract

La présente invention concerne une composition pour prévenir, soulager ou traiter un cancer. Plus précisément, la présente invention concerne une composition pharmaceutique contenant, comme principe actif, un extrait mélangé d'aune japonais, de sagesse-des-chirurgiens et de Peucedanum praeruptorum, ou une fraction associée pour prévenir ou traiter un cancer ; une composition d'aliment sain fonctionnel contenant, comme principe actif, l'extrait mélangé d'aune japonais, de sagesse-des-chirurgiens et de Peucedanum praeruptorum, ou la fraction associée pour prévenir ou soulager un cancer ; et un procédé pour prévenir ou traiter un cancer à l'aide de la composition.
PCT/KR2014/007537 2013-10-28 2014-08-13 Composition contenant, comme principe actif, un extrait mélangé d'aune japonais, de sagesse-des-chirurgiens et de peucedanum praeruptorum, ou une fraction associée pour prévenir ou traiter un cancer WO2015064899A1 (fr)

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KR1020130128792A KR101533733B1 (ko) 2013-10-28 2013-10-28 오리나무, 재쑥 및 백화전호의 혼합 추출물 또는 이의 분획물을 유효 성분으로 함유하는 암의 예방 또는 치료용 조성물

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KR102137388B1 (ko) * 2018-11-22 2020-07-24 동의대학교 산학협력단 오리나무열매 추출물 또는 이의 분획물을 유효성분으로 포함하는 암의 예방 또는 치료용 조성물
KR102318928B1 (ko) * 2019-11-12 2021-10-28 국립낙동강생물자원관 물오리나무 추출물을 유효성분으로 포함하는 암 전이 억제용 조성물
KR102565622B1 (ko) * 2021-03-23 2023-08-14 연세대학교 산학협력단 뇌암의 예방 또는 치료용 조성물

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KR20100007377A (ko) * 2008-07-14 2010-01-22 김춘성 바디나물 추출물을 포함하는 항암제 조성물

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