[go: up one dir, main page]

WO2014042355A1 - Composition pharmaceutique pour inhiber le cancer ou la métastase contenant un extrait de quassia undulata ou une fraction de celui-ci comme principe actif - Google Patents

Composition pharmaceutique pour inhiber le cancer ou la métastase contenant un extrait de quassia undulata ou une fraction de celui-ci comme principe actif Download PDF

Info

Publication number
WO2014042355A1
WO2014042355A1 PCT/KR2013/006739 KR2013006739W WO2014042355A1 WO 2014042355 A1 WO2014042355 A1 WO 2014042355A1 KR 2013006739 W KR2013006739 W KR 2013006739W WO 2014042355 A1 WO2014042355 A1 WO 2014042355A1
Authority
WO
WIPO (PCT)
Prior art keywords
cancer
undulata
extract
fraction
inhibiting
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/KR2013/006739
Other languages
English (en)
Korean (ko)
Inventor
권병목
한동초
박상홍
이중구
전윤정
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.)
Korea Research Institute of Bioscience and Biotechnology KRIBB
Original Assignee
Korea Research Institute of Bioscience and Biotechnology KRIBB
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
Application filed by Korea Research Institute of Bioscience and Biotechnology KRIBB filed Critical Korea Research Institute of Bioscience and Biotechnology KRIBB
Publication of WO2014042355A1 publication Critical patent/WO2014042355A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/20—Ingredients acting on or related to the structure
    • A23V2200/21—Binding agent
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/308—Foods, ingredients or supplements having a functional effect on health having an effect on cancer prevention
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/326—Foods, ingredients or supplements having a functional effect on health having effect on cardiovascular health
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2300/00—Processes
    • A23V2300/14—Extraction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps

Definitions

  • a pharmaceutical composition for inhibiting cancer or cancer metastasis comprising an extract of Quecia Undulata or a fraction thereof as an active ingredient.
  • the present invention relates to a composition for treating cancer or inhibiting cancer metastasis, comprising a Quecia Undulata extract or a fraction thereof as an active ingredient, and more specifically, using water, alcohol or a mixture thereof as a solvent.
  • the present invention relates to a pharmaceutical composition for preventing or treating cancer, or inhibiting cancer metastasis, or a pharmaceutical composition for inhibiting angiogenesis, comprising an extract of the root of Quebec Undulata extracted, or an active fraction thereof.
  • Cancer is a general group of diseases that can start by uncontrolled cell proliferation, invade and destroy new surroundings and create new growth sites. Last 10 or so. Despite years of remarkable advances in the regulation of cell cycles and apoptosis and the search for new targets, including oncogenic and cancer suppressor genes, in order to conquer cancer, the incidence of cancer has evolved as civilization develops. It is increasing. Currently, the treatment of cancer patients relies on chemotherapy by surgical surgery, radiation therapy and the administration of over 40 types of cytotoxic drugs, most of which are limited to early cancer patients or certain cancers. Deaths are on the rise. On the other hand, cancer is the life-threatening cause of cancer metastasis, and most deaths from cancer are explained by cancer metastasis.
  • Surgical surgery is currently a clinically proven universal treatment for cancer, but Even if the cancer is removed, cancer cells that have metastasized to other tissues become difficult to treat. Thus, cancer conquest is actually a fight against cancer metastasis.
  • Cell migration in cancer metastasis is involved in several stages, where the cancer cells are involved in extracellular matr ix (ECM) at the initial primary cancer site. The process is very complicated and involved, such as when moving to the blood vessels, when moving out of the blood vessels in the second metastasis tissue, and when the vascular endothelial cells in the neovascular vessels (mobile endothelial cells).
  • Migrating cells are polarized by signal receptors activated by cell migration inducers.
  • the front end of the cell is extended to the cell membrane by the polymerization of actin (act in) and attached to the interstitial cell through integrin.
  • actin actin
  • a strong contraction force is formed between actin polymers by myosin coupled to the actin polymer, and a strong contraction force is given to the entire cell. Therefore, the direction of cell migration is determined by the difference in adhesion between the front and rear parts of the cell. If the attachment force of the newly formed front is greater than the adhesion of the back, the rear part of the cell is separated from the interstitial cells, and the cell is moved forward, and vice versa, the cell stays in its original position.
  • Structural morphologically different cell protrusions are formed depending on the signaling molecules activated by the cell transduction signal receptor. Not only do these different overhangs include the actual actin, but they also contain a diverse set of structural and signal proteins and lead to dynamic interactions with ECM (Peter Friedl, et al. Nature Cancer Review, 2003, 3: 362).
  • Anticancer agents that target cancer cell migration are aimed at suppressing cancer metastasis.
  • Cell migration inhibitors are not the best targets, but they are a realistic approach to extending the lives of cancer patients we pursue. Actually cancer Regardless of where it occurs, finding only the production site can be easily removed by surgical procedures.
  • cancer cell can spread to other areas than the primary cancer site. You can expect However, if the cancer is not diagnosed early, the cancer cells have already spread through the blood vessels and formed very small colonies in the second or third position. Cannot be cured successfully. In fact, in many cases cancer cells metastasize and give up surgical treatment. In this case, cancer cell death is prevented by administering an anticancer agent while inhibiting cancer cell migration to prevent further spread of metastasis, thereby prolonging the patient's life. It may help you. Therefore, the development of cancer cell migration inhibitors can be developed as a new concept of anticancer drugs, and the identified inhibitors can be used as important materials for academic research on cell migration.
  • Angiogenesis refers to the process of formation of new blood vessels from existing vessels, which are essential for the metastasis of cancer during development of malignancies (Jack 1. Arbiser, et al., Proc Natl.Aced.Sci. USA, 1997, 94: 861). Recently, as an anti-cancer drug development method, such angiogenesis inhibitors are attracting attention. Firstly, angiogenesis is essential in primary or metastatic tumors, and cancer tissues are 1-2 or more without nutrient and oxygen supply by neovascularization. Unable to grow (J. Folkman. Sewin Cancer Biol., 1992, 3:65). During angiogenesis, primary cancer cells enter the blood vessels and migrate to other sites to form metastatic cancer.
  • angiogenesis inhibitors can be commonly used in all sol id tumors.
  • conventional anti-cancer chemotherapy treats cancer cells to grow rapidly. Therefore, they exhibit cytotoxicity to bone marrow cells and gastrointestinal cells, which have a relatively rapid cell cycle, whereas angiogenesis inhibitors are used for long-term administration. Even relatively few side effects can be present.
  • chemotherapy may show new resistance because it targets cancer cells that have been transformed, but angiogenesis inhibitors are less likely to be resistant in that normal blood cells are the target of treatment.
  • one blood vessel cell supplies nutrients and oxygen to hundreds of cancer cells, it can be an effective treatment method for inhibiting many cancer cells through inhibition of one blood vessel cell.
  • the anticancer drug is leaked out of the blood vessels to affect cancer cells, whereas the angiogenesis inhibitor acts by directly contacting the vascular endothelial cells to facilitate drug delivery.
  • angiostatin one of the angiogenesis inhibitors, has been shown to prevent the metastasis and growth of lung cancer cells (MS 0'Relly, et al., Cell, 1994, 79: 715).
  • the substance, called genistein, is expected to be able to inhibit the growth of small malignancies. Japanese people eat more soy, so the incidence of prostate cancer is much lower than in Westerners. However, it is reported that the frequency of prostate cancer increases rapidly if Japanese do not eat soy during just a few years after emigrating to the West (FM Uckun, et al., Science, 1995 267: 886). In 1995, Dr. Faith M. Uckun's team at the University of Minnesota, USA, administered a drug that cross-linked Genistein to a monoclonal antibody to mice transplanted with human BCP leukemia cells, surprisingly 99.999% of human BCP leukemia cells.
  • the present inventors have found a root extract of Quescia Undulata or a fraction thereof having both inhibitory activity of cell migration and angiogenesis-inhibitory activity related to cancer metastasis.
  • the root extract of Quescia Undulata or a fraction thereof The present invention was completed by confirming that there is an effect of inhibiting metastasis by inhibiting cancer cell migration and inducing death of cancer cells.
  • An object of the present invention is a composition for preventing and treating cancer, a composition for inhibiting cancer metastasis, a composition for inhibiting angiogenesis, or preventing and improving cancer, comprising an extract of the root of Quescia undulata or an active fraction thereof. To provide health food for.
  • the present invention provides a pharmaceutical composition for inhibiting cancer or cancer metastasis containing quecia Undulata (ft / ass / a undulata) extract or a fraction thereof as an active ingredient.
  • the present invention provides a pharmaceutical composition for inhibiting neovascular formation, containing Quecia Undulata extract or a fraction thereof as an active ingredient.
  • the present invention also provides a pharmaceutical composition for the prevention and treatment of diseases caused by neovascularization containing Quecia Undulata extract or fractions thereof as an active ingredient.
  • the present invention provides a health food for inhibiting cancer or cancer metastasis containing Quecia Undulata extract or a fraction thereof as an active ingredient.
  • the present invention provides a health food for inhibiting neovascularization containing Quecia Undulata extract or a fraction thereof as an active ingredient.
  • the present invention provides a health food for the prevention and improvement of diseases caused by neovascularization containing Quecia Undulata extract or a fraction thereof as an active ingredient.
  • the present invention also provides a method for treating cancer, comprising administering a pharmaceutically effective amount of Quescia Undulata extract or a fraction thereof to a subject with cancer.
  • the present invention also provides a method for inhibiting cancer metastasis, comprising administering a pharmaceutically effective amount of Quexia Undulata extract or a fraction thereof to a subject with cancer.
  • the present invention also provides a method for preventing cancer, comprising administering to a subject a pharmaceutically effective amount of Quescia Undulata extract or a fraction thereof.
  • the present invention also provides a method for inhibiting angiogenesis, comprising administering to a subject a pharmaceutically effective amount of Quescia Undulata extract or a fraction thereof.
  • the present invention also provides the use of a quesaundulata extract or a fraction thereof for use as a pharmaceutical composition for preventing and treating cancer.
  • the present invention also provides the use of Quecia Undulata extract or fractions thereof for use as a health food for preventing and improving cancer.
  • the present invention also provides the use of Quecia Undulata Extract or a fraction thereof for use as a health food for inhibiting angiogenesis.
  • the present invention relates to a composition for inhibiting cancer or cancer metastasis containing the extract of Quescia Undulata (/ ass / a iindulata) or a fraction thereof as an active ingredient, and more specifically, using water, alcohol or a mixture thereof as a solvent. Extracts from the roots of Quescia Undulata or fractions thereof are found to be effective in inhibiting the growth of cancer cells, inhibiting cancer cell migration and inhibiting the formation of vascular endothelial cells (HUVECs) that play an important role in the formation of angiogenesis. By doing so, it can be usefully used as a composition for inhibiting cancer or cancer metastasis, and a composition for inhibiting neovascularization.
  • UAVECs vascular endothelial cells
  • 1 is a diagram confirming the migration inhibitory activity of cells in the colorectal cancer cell line (D1D-1) treated with quessa Undulata extract.
  • Figure 2 is a diagram showing the cell migration inhibitory activity in cell lines D1D-KPR ⁇ 3), D1D-1, myeloma cell line A375P, prostate cancer cell line DU145 and pancreatic cancer cell line Miapaca2 treated with Quescia Undulata fraction.
  • Figure 3 is a diagram confirming the migration inhibitory activity of cells in the colorectal cancer cell line D1D-KPR1-3 treated with Quescia Undulata fraction.
  • FIG. 4 is a diagram showing the effect of inhibiting the tube formation of the cells in vascular endothelial cells (HUVEC) treated with Quescia Undulata fraction.
  • anticancer used in the present invention means the action of inhibiting the formation or proliferation of cancer cells or inhibiting or blocking the action of killing cancer cells, and means the prevention and treatment of cancer.
  • prevention means any action that inhibits cancer formation or delays the onset by administration of a composition of the present invention.
  • treatment and “improvement” refer to any action by which administration of the composition of the present invention improves or advantageously alters the symptoms of the disease.
  • administration means providing a patient with a given composition of the present invention in any suitable manner.
  • the term "patient” refers to any animal, such as a human, monkey, dog, goat, pig or rat, having a disease that can improve symptoms by administering the composition of the present invention.
  • the term "pharmaceutically effective amount” means an amount sufficient to treat a disease at a reasonable benefit or risk ratio applicable to medical treatment, which is the type of disease, severity, activity of the drug, drug Sensitivity to, time of administration, route of administration and rate of administration, duration of treatment, factors including concurrently used drugs, and other factors well known in the medical arts.
  • the present invention will be described in detail.
  • the present invention provides a pharmaceutical composition for preventing and treating cancer containing Quecia Undulata extract as an active ingredient.
  • the extract may be extracted from the root of Quecia Undulata, but is not limited thereto.
  • the extract may be extracted using water, d to C 2 lower alcohol or a mixture thereof as a solvent, but is not limited thereto.
  • the lower alcohol may be methane or ethane, but is not limited thereto.
  • the Quecia Undulata extract may be prepared by a manufacturing method including the following steps, but is not limited thereto.
  • step 3 drying the filtered extract of step 2) under reduced pressure.
  • the quecia undulata of step 1) can be used without limitation, such as cultivated or commercially available.
  • the quecia undulata may be one using the root of the quecia undulata, but is not limited thereto.
  • a conventional method in the art such as filtration, hot water extraction, immersion extraction, reflux angle extraction, and ultrasonic extraction, may be used to extract 1 to 5 times by hot water extraction.
  • the extraction may be performed three times more specifically, but is not limited thereto.
  • the extraction solvent may be added 0.1 to 10 times to the dried Quecia Undulata, preferably 3 to 5 times.
  • the extraction temperature may be 20 to 40, but is not limited thereto.
  • the extraction time may be 12 to 48 hours, but is not limited thereto.
  • the decompression concentration in step 3) may be to use a vacuum decompression concentrator or a vacuum rotary evaporator, but is not limited thereto.
  • the drying may be to dry under reduced pressure, vacuum drying, boiling drying, spray drying or freeze drying, but is not limited thereto.
  • the fraction is obtained by converting Quecia Undulata methanol extract into 50% to 100% methane.
  • the extracted active fraction may be additionally included as an active ingredient, but is not limited thereto. .
  • the cancer may be selected from the group consisting of colon cancer, stomach cancer, prostate cancer, breast cancer, kidney cancer, liver cancer, brain tumor, lung cancer, uterine cancer, colon cancer, bladder cancer, or pancreatic cancer, but is not limited thereto.
  • a pharmaceutical composition for inhibiting angiogenesis comprising an extract of Quecia Undulata (ft / ass / a unduJata) or a fraction thereof as an active ingredient.
  • the extract may be extracted from the root of Quecia Undulata, but is not limited thereto.
  • the extract may be extracted with water, a lower alcohol of d to C 2 or a mixture thereof, but is not limited thereto.
  • the lower alcohol may be methanol or ethane, but is not limited thereto.
  • the Quecia Undulata extract may be prepared by a manufacturing method including the following steps, but is not limited thereto.
  • step 3 drying the filtered extract of step 2) under reduced pressure.
  • the quecia undulata of step 1) can be used without limitation, such as cultivated or commercially available.
  • the quecia undulata may be one using the root of the quecia undulata, but is not limited thereto.
  • Extraction method of the Quescia Undulata extract may be used in the art, such as filtration, hot water extraction, immersion extraction, reflux angle extraction and ultrasonic extraction, and may be one to five times by the hot water extraction method In this case, the extraction may be performed three times more specifically, but is not limited thereto.
  • the extraction solvent may be added 0.1 to 10 times to the dried Quecia Undulata, preferably 0.3 to 5 times.
  • the extraction temperature may be 20 to 40, but is not limited thereto.
  • the extraction time may be 12 to 48 hours However, it is not limited thereto.
  • the decompression concentration in step 3) may be to use a vacuum decompression concentrator or a vacuum rotary evaporator, but is not limited thereto.
  • the drying may be to dry under reduced pressure, vacuum drying, boiling drying, spray drying or freeze drying, but is not limited thereto.
  • the fraction may include, but is not limited to, an active fraction further extracted with queciaundulata methanol extract with 50% to 100% methanol as an active ingredient.
  • the disease caused by neovascularization may be selected from the group consisting of diabetic retinopathy, rheumatoid arthritis, chronic inflammation, and hemangioma, but is not limited thereto. It provides a pharmaceutical composition for the prevention and treatment of diseases caused by neovascularization containing Quecia Undulata extract (ft / ass / undid at a) or a fraction thereof as an active ingredient.
  • Quecia Undulata extract ft / ass / undid at a
  • the extract may be extracted from the root of Quecia Undulata, but is not limited thereto.
  • the disease caused by the neovascularization may be selected from the group consisting of diabetic retinopathy, rheumatoid arthritis, chronic inflammation and hemangioma, but is not limited thereto.
  • the inventors of the present invention utilize a cellular child assay that can confirm cell migration under a microscope using a modified Boyden chamber.
  • the degree of cell migration inhibition of colorectal cancer cell line [D1D-KPR ⁇ 3)] was measured in other root extracts. As a result, more than 90% cell migration inhibitory activity was confirmed in 10 ug / ml of Quecia Undulata extract (see Figure 1).
  • the present inventors have investigated in vivo endothelial cells that can observe neovascularization indirectly in vitro using vascular endothelial cells (HUVECs) to investigate the effects of Quecia Undulata root extract or fractions thereof on cell migration.
  • a endothelial morphogenesis assay was performed. As a result, it was confirmed that the Quebec Undulata extract or fractions thereof having an excellent platelet inhibitory activity by inhibiting the formation (tube formation) at a concentration of 5ug / ml (see Figure 4).
  • Quescia Undulata root extract and fractions thereof of the present invention were confirmed to be effective in inhibiting vascular endothelial cell (HUVEC) tube formation, which plays an important role in inhibiting cancer cell growth, inhibiting cancer cell migration and forming angiogenesis. .
  • it may be usefully used as a composition for inhibiting cancer metastasis and a composition for inhibiting neovascularization have.
  • the composition for preventing and treating cancer of the present invention may contain Quecia Undulata extract, an active fraction thereof, or a combination thereof, and may contain one or more active ingredients exhibiting the same or similar functions in addition to the above components. have.
  • Quecia Undulata extract of the present invention can be administered orally or parenterally during clinical administration and can be used in the form of general pharmaceutical preparations. That is, the composition of the present invention may be administered in various oral and parenteral dosage forms in actual clinical administration, and when formulated, it is used as a diluent such as fillers, bulking agents, binders, wetting agents, disintegrating agents, and surfactants that are commonly used. Formulated using excipients.
  • Solid preparations for oral administration include tablets, pills, powder granules and capsules, and the like, which may be used in the pharmaceutical compositions of the present invention at least one excipient such as starch, calcium carbonate, sucrose, lactose and It is prepared by mixing gelatin. In addition to simple excipients, lubricants such as magnesium styrate talc are also used.
  • Liquid preparations for oral administration include suspensions, solutions, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to the commonly used simple diluents, water and liquid paraffin.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and 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, hemp trigol, tween 61, cacao butter, laurin butter, glycerol and gelatin can be used.
  • the composition of the present invention may be via subcutaneous injection, intravenous injection or intramuscular injection during parenteral administration.
  • the dosage unit may contain, for example, 1, 2, 3 or 4 times the individual dosage or 172, 1/3 or 1/4 times.
  • the individual dosage preferably contains the amount in which the effective drug is administered at one time, which is usually one half of the daily dose, Equivalent to 1/3 or 1/4 times
  • the effective dose of the composition of the present invention is 0.01 to 10 g / kg, preferably 0.1 g to 5 g / kg, may be administered 1 to 6 times a day.
  • the dosage may be increased or decreased depending on the route of administration, the severity of the disease, sex, congestion, and age, and thus the above dosage does not limit the scope of the present invention in any way.
  • the 50% lethal dose (1D 50 ) by the oral dose toxicity test is determined to be a safe substance of at least 1 g / kg or more.
  • the compositions of the invention can be used in combination with either alone, or surgery, hormone therapy, chemical therapy, and how to use the biological control agent banung for cancer prevention and treatment.
  • the present invention provides a health food for inhibiting cancer or cancer metastasis containing Quecia Undulata ⁇ / ⁇ / ⁇ undulata) extract or a fraction thereof as an active ingredient.
  • the cancer may be selected from the group consisting of colon cancer, stomach cancer, prostate cancer, breast cancer, kidney cancer, liver cancer, brain tumor, lung cancer, uterine cancer, colon cancer, bladder cancer or pancreatic cancer, but is not limited thereto.
  • Quecia Undulata provides a health food for inhibiting neovascular formation containing an extract or a fraction thereof as an active ingredient.
  • the disease caused by the neovascularization may be selected from the group consisting of diabetic retinopathy, rheumatoid arthritis, chronic inflammation and hemangioma, but is not limited thereto.
  • an active fraction thereof or a mixture thereof as a food additive the extract, fraction or mixture may be added as it is or used in combination with other food or food ingredients, It can be suitably used according to a conventional method.
  • the Quecia Undulata extract is preferably extracted using hot water and ethane, and the concentration of ethane is preferably 50% to 70%.
  • the mixed amount of the active ingredient can be determined suitably according to the purpose of use (prevention, health or therapeutic treatment).
  • the composition of the present invention is added in an amount of up to 15 parts by weight, preferably up to 10 parts by weight based on the raw materials.
  • the amount may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety.
  • the kind of food There is no particular limitation on the kind of food.
  • foods to which the Quecia Undulata extract of the present invention, an active fraction thereof, or a combination thereof may be added include meat, sausage, bread, chocolate, candy, snacks, confectionary, pizza, ramen, other noodles, 3 ⁇ 4, Dairy products, including ice cream, various soups, beverages, tea, drinks, alcoholic beverages and vitamin complexes, and includes all healthy foods in the usual sense.
  • the health beverage composition of the present invention may contain various flavors or natural carbohydrates, etc. as additional components, as in the general beverage.
  • Natural carbohydrates are sugars such as glucose, monosaccharides such as fructose, malsaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, xylyl, sorbitol and erythritol.
  • sweetener natural sweeteners such as tautin, stevia extract, synthetic sweeteners such as saccharin, aspartame, and the like can be used.
  • the ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g, per 1 composition 100 of the present invention.
  • the active fractions thereof, or a combination thereof may be used in various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages and the like.
  • Else the active fractions of Haccia undulata extract of the present invention or Mixtures thereof may contain pulp for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components can be used independently or in combination.
  • the present invention also provides a method for treating cancer, comprising administering a pharmaceutically effective amount of Quescia Undulata extract or a fraction thereof to a subject with cancer.
  • the present invention also provides a method for preventing cancer, comprising administering to a subject a pharmaceutically effective amount of Cercia undulata extract or a fraction thereof.
  • the present invention also provides a method for inhibiting cancer metastasis, comprising administering a pharmaceutically effective amount of Quessa Undulata extract or a fraction thereof to a subject with cancer.
  • the present invention also provides a method for inhibiting angiogenesis, comprising administering to a subject a pharmaceutically effective amount of Quescia Undulata extract or a fraction thereof.
  • the pharmaceutically effective amount is 0001 to 100 nig / kg, preferably 0.001 to 10 nig / kg, but is not limited thereto. Dosage may vary depending on the weight, age, sex, health status, diet, duration of administration, rate of administration, elimination rate, and severity of the particular patient.
  • the pharmaceutical composition may be administered orally or parenterally during clinical administration and intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, intramuscular injection, intrauterine dural injection, cerebrovascular injection, or thoracic injection during parenteral administration. It can be administered by internal injection and can be used in the form of ' general pharmaceutical formulations.
  • the Quescia Undulata root extract of the present invention or a fraction thereof has been shown to inhibit vascular endothelial cell (HUVEC) tube formation, which plays an important role in inhibiting cancer cell growth, inhibiting cancer cell migration, and angiogenesis,
  • vascular endothelial cell (HUVEC) tube formation which plays an important role in inhibiting cancer cell growth, inhibiting cancer cell migration, and angiogenesis
  • the present invention also provides the use of Quecia Undulata extract or fractions thereof for use as a pharmaceutical composition for the prevention and treatment of cancer.
  • the Quescia Undulata root extract of the present invention or fractions thereof inhibits vascular endothelial cell (HUVEC) tube formation, which plays an important role in inhibiting cancer cell growth, inhibiting cancer cell migration, and angiogenesis
  • the Quescia Undulata root Root extract or a fraction thereof may be usefully used as a therapeutic pharmaceutical composition containing as an active ingredient.
  • the present invention also provides the use of Quecia Undulata extract or a fraction thereof for use as a health food for preventing and improving cancer.
  • the present invention also provides the use of Quecia Undulata extract or a fraction thereof for use as a health food for preventing and improving cancer.
  • the Quescia Undulata root extract of the present invention or fractions thereof inhibits vascular endothelial cell (HUVEC) tube formation, which plays an important role in inhibiting cancer cell growth, inhibiting cancer cell migration, and angiogenesis
  • the Quescia Undulata root It can be usefully used as a therapeutic composition and cancer preventive health functional products containing the root extract or fractions thereof as an active ingredient.
  • the present invention will be described in detail by Examples, Experimental Examples and Preparation Examples. However, the following Examples, Experimental Examples, and Production Examples specifically illustrate the present invention, and the content of the present invention is not limited to Examples, Experimental Examples, and Production Examples.
  • Example ⁇ 1-1> 7 g of the methanol extract of Quescia Undulata root obtained in Example ⁇ 1-1> was dissolved in 50 ml of methane and adsorbed onto 500 g of C18, followed by 50% methanol, 70% methane and 100% methanolol, respectively. Elution was carried out sequentially using 1 to obtain 660 mg of fraction 1 (methanol and water 1: 1 elution fraction) and 330 mg of fraction 2 (methane and water 2: 1 elution fraction).
  • the modified Boyden chamber Neuro Probe
  • 8 ⁇ pore-sized membrane membrane, neuro probe
  • staining solution required for cell staining Kimja stain Kimja stain
  • the necessary experimental equipment was a C0 2 incubator (Thermo Forma, Germany) required for cell culture, a centrifuge to wash the cells and an inverted microscope (TE 300, Nikon, Japan) to observe the results.
  • the prepared cells were then placed in the wells of the top plate by 50 ⁇ .
  • the chamber was wrapped and incubated for 18 hours in 37 and> C0 2 incubators. After 15 to 24 hours, depending on the cancer cells, the nuts were removed, the membranes were separated, fixed in methanol for 10 minutes, and dried in air. The membrane was dried and dyed for 90 minutes in the Kimja solution, a dyeing reagent. At this time, the dyeing reagent was used was distilled water and distilled in 1:10 ratio. After staining, the cells were soaked in distilled water for about 10 seconds. The membrane was placed on a cover slip with the cells not moving upwards and wiped with a cotton swab.
  • the inventors of the present invention used an in vivo endothelial morphogenesis assay to determine the effect of Quecia Undulata extract or fractions thereof on cell migration.
  • vascular endothelial cells vascular endothelial cells
  • HAVECsXATCC vascular endothelial cells
  • 24-well 1 cell culture plates and matrigel matrix D biosciences
  • an inverted microscope equipped with a digital camera TE 300, Nikon, Japan
  • TE 300, Nikon, Japan was used to observe the C0 2 incubator for culturing cells and to confirm the results.
  • Endothelial cells (HUVECs) were prepared by starvation overnight using serum-free medium.
  • vascular endothelial cells were formed using an inverted microscope for the degree of inhibition of tube formation in forming a tube shape.
  • Example 2 Quecia Undulata Root 50% Methane Fraction 1 g Corn Starch 5 g Carboxy Cellose 4.9 g After mixing the above components to prepare a powder, the powder is prepared in a conventional 3 ⁇ 4 capsule To prepare a capsule by filling into a hard capsule according to.
  • Example 2 Quercia Undulata Root 70% Methanol Fraction 0.1 g Injectable Sterile Distilled Water Amount of H Regulator Amount Suitable for the preparation of the above components per ampule (2 mi) according to the conventional method for preparing an injection.
  • Example 2 100% Cyanciaundulata Root 100% Methane Fraction 0.1 g Isomerized Sugar 10 g Manntle 5 g Enteric Water Appropriate According to the conventional method for preparing a liquid solution, each of the ingredients in water is dissolved and lemon flavor is added. An appropriate amount was added and then the above ingredients were mixed. Then, purified water was added thereto to adjust the total amount to 100, and then layered into brown bottles to sterilize to prepare a liquid. . Production Example 2 Preparation of Health Food
  • Example ⁇ 1-3> 0.5 to 5.0 parts by weight of the Quescia Undulata Root Hydrothermal Extract of Example ⁇ 1-3> was added to the flour, and bread, cake, cookies, crackers, and noodles were prepared using this mixture.
  • Quenchia Undulata root hot water extract of Example ⁇ 1-3> was added to the soup and juice to increase the weight of the meat products for health promotion, soup and noodles of juice.
  • Example ⁇ 1-3> 5-10 parts by weight of the Quescia Undulata Root Hydrothermal Extract of Example ⁇ 1-3> was added to milk, and various dairy products such as butter and ice cream were prepared using the milk.
  • Brown rice, barley, glutinous rice, yulmu was alphad by a known method, and then dried and roasted to prepare a powder having a particle size of 60 mesh.
  • Black beans, black sesame seeds, and sesame seeds were also steamed and dried in a known manner, and then roasted to prepare a powder having a particle size of 60 mesh.
  • the Quescia Undulata Root Hot Water Extract of Example ⁇ 1-3> was concentrated under reduced pressure in a vacuum concentrator, dried by spraying and drying with a hot air dryer, and then pulverized with a particle size of 60 mesh to obtain a dry powder.
  • the grains, seeds and the Undulata root hydrothermal extract of Example ⁇ 1-3> prepared above were combined and prepared in the following ratio.
  • Seeds (7 parts by weight perilla, 8 parts by weight black beans, 7 parts by weight black sesame seeds),
  • composition ratio was mixed with relatively suitable ingredients for the preferred beverage in the preferred embodiment, the blending ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and use purpose.
  • the present invention is composed of colon cancer, gastric cancer, prostate cancer, breast cancer, kidney eye, liver cancer, brain tumor, lung cancer, uterine cancer, colon cancer, bladder cancer and pancreatic cancer containing pancreatic undulata extract or fractions thereof as an active ingredient. It may be usefully used for cancer-charging and therapeutic pharmaceutical compositions selected from the group or pharmaceutical compositions for inhibiting neovascularization.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Botany (AREA)
  • General Chemical & Material Sciences (AREA)
  • Mycology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biotechnology (AREA)
  • Medical Informatics (AREA)
  • Microbiology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Epidemiology (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Oncology (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

La présente invention concerne une composition visant à inhiber le cancer ou la métastase, contenant un extrait de Quassia undulata ou une fraction de celui-ci comme principe actif. De manière plus spécifique, un extrait de racines de Quassia undulata extraites à l'eau, un alcool ou un mélange de celui-ci utilisé comme solvant, ou une fraction de celui-ci ont été identifiés pour inhiber la prolifération de cellules cancéreuses, inhiber la métastase de cellules cancéreuses et inhiber la formation d'un tube de cellules endothéliales de veine de cordon ombilical humain (HUVEC) qui joue un rôle important dans l'angiogenèse, cette composition pouvant donc être utile pour inhiber le cancer ou la métastase ou pour inhiber l'angiogenèse.
PCT/KR2013/006739 2012-09-17 2013-07-26 Composition pharmaceutique pour inhiber le cancer ou la métastase contenant un extrait de quassia undulata ou une fraction de celui-ci comme principe actif Ceased WO2014042355A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2012-0102685 2012-09-17
KR1020120102685A KR20140036513A (ko) 2012-09-17 2012-09-17 퀘시아 운둘라타의 추출물 또는 이의 분획물을 유효성분으로 함유하는 암 또는 암 전이 억제용 약학적 조성물

Publications (1)

Publication Number Publication Date
WO2014042355A1 true WO2014042355A1 (fr) 2014-03-20

Family

ID=50278428

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2013/006739 Ceased WO2014042355A1 (fr) 2012-09-17 2013-07-26 Composition pharmaceutique pour inhiber le cancer ou la métastase contenant un extrait de quassia undulata ou une fraction de celui-ci comme principe actif

Country Status (2)

Country Link
KR (1) KR20140036513A (fr)
WO (1) WO2014042355A1 (fr)

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
ADESANWO, J. K. ET AL.: "Antimicrobial and cytotoxic activity of the stem and root bark extracts of Quassia undulata and isolated constituents", TOXICOLOGICAL & ENVIRONMENTAL CHEMISTRY, vol. 91, no. 5, 2009, pages 999 - 1003 *
CACHET, N. ET AL.: "Antimalarial activity of simalikalactone E, a new quassinoid from Quassia amara L. (Simaroubaceae)", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 53, no. 10, 2009, pages 4393 - 4398 *
FERRARI, A. ET AL.: "Evaluation of the efficacy and tolerance of a topical gel with 4% Quassia extract in the treatment of rosacea", THE JOURNAL OF CLINICAL PHARMACOLOGY, vol. 52, no. 1, January 2012 (2012-01-01), pages 84 - 88 *
HUSAIN, G. M. ET AL.: "Antidiabetic activity of standardized extract of Quassia amara in nicotinamide-streptozotocin-induced diabetic rats", PHYTOTHERAPY RESEARCH, vol. 25, 2011, pages 1806 - 1812 *

Also Published As

Publication number Publication date
KR20140036513A (ko) 2014-03-26

Similar Documents

Publication Publication Date Title
US8753694B2 (en) Anti-angiogenic agents and anti-obesity substances applied with anti-angiogenesis from natural products
KR101416149B1 (ko) Ｉｌ－６ 유도 ｓｔａｔ３ 활성화 저해 효과를 갖는 강황 또는 울금의 지상부 추출물, 또는 이의 비극성 유기용매 분획물을 포함하는 조성물
KR102558650B1 (ko) 해마 및 한약재 혼합 추출물을 유효성분으로 함유하는 전립선암의 예방, 개선 또는 치료용 조성물
KR101579820B1 (ko) 퀘시아 운둘라타의 추출물 또는 이의 분획물을 유효성분으로 함유하는 암 또는 암 전이 억제용 약학적 조성물
KR20110114346A (ko) 비파 추출물을 유효성분으로 포함하는 항암 조성물
KR102002260B1 (ko) 마늘 추출 분획물로부터 분리된 화합물을 유효성분으로 함유하는 근육관련 질환 치료 및 예방용 조성물
KR20180131770A (ko) 황련 추출물을 함유하는 근육관련 질환의 예방 및 치료용 조성물
KR102815360B1 (ko) 암의 예방 또는 치료용 조성물
KR101720610B1 (ko) Ｓｔａｔ３ 저해활성을 갖는 토목향 헥산 분획물 또는 이로부터 분리된 화합물을 유효성분으로 함유하는 유방암 예방 및 치료용 약학적 조성물
KR20230122810A (ko) 측백엽 추출물을 포함하는 자가포식 억제용 조성물
WO2014042355A1 (fr) Composition pharmaceutique pour inhiber le cancer ou la métastase contenant un extrait de quassia undulata ou une fraction de celui-ci comme principe actif
KR101392345B1 (ko) 영릉향 추출물을 유효성분으로 함유하는 항암용 약학조성물
KR101099651B1 (ko) 개상사화 추출물을 유효성분으로 함유하는 암 예방 및 치료용 또는 혈관신생 억제용 약학적 조성물
KR20220063029A (ko) 한약복합추출물을 포함하는 악액질 예방 또는 치료용 조성물
KR20210057657A (ko) 월견초 추출물을 유효성분으로 함유하는 종양증식 억제용 조성물
KR20090110602A (ko) 일본 후박나무 추출물 또는 이의 분획물을 유효성분으로함유하는 암 치료 및 암전이 억제용 조성물
KR20210083631A (ko) 바이칼레인을 함유하는 암성 악액질 예방, 개선 또는 치료용 조성물
JP5985062B2 (ja) アルトカルプス・アルティリスの果実、葉、若しくは幹の抽出物、又はそれらの画分を有効成分として含有するがんの予防又は治療のための組成物
KR101185901B1 (ko) 등골나물 추출물을 포함하는 항암 조성물
KR102448274B1 (ko) 보골지 추출물의 조다당 분획물을 유효성분으로 함유하는 골질환의 예방, 개선 또는 치료용 조성물
KR102298385B1 (ko) 바닐릭산을 함유하는 암성 악액질 예방, 개선 또는 치료용 조성물
KR20250113581A (ko) 편백 추출물을 포함하는 항암용 조성물
KR101215797B1 (ko) 뽕나무 추출물을 유효성분으로 함유하는 간경화증의 예방 및 치료용 조성물
KR102156701B1 (ko) 달맞이꽃 추출물을 유효성분으로 포함하는 암 전이 억제용 조성물
KR20250014243A (ko) 과루인 추출물을 유효성분으로 포함하는 암의 예방 또는 치료용 조성물

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 13836993

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 13836993

Country of ref document: EP

Kind code of ref document: A1