WO2014042355A1 - Pharmaceutical composition for inhibiting cancer or metastasis, containing quassia undulata extract or fraction thereof as active ingredient - Google Patents

Abstract

The present invention relates to a composition for inhibiting cancer or metastasis, containing a Quassia undulata extract or a fraction thereof as an active ingredient. More specifically, an extract of Quassia undulata roots extracted by using water, an alcohol or a mixture thereof as a solvent, or a fraction thereof has been ascertained to inhibit the growth of cancer cells, inhibit the metastasis of cancer cells, and inhibit the formation of a human umbilical vein endothelial cell (HUVEC) tube, which plays an important role in angiogenesis, and thus can be useful as a composition for inhibiting cancer or metastasis or as a composition for inhibiting angiogenesis.

Description

 [Specification】

 [Name of invention]

 A pharmaceutical composition for inhibiting cancer or cancer metastasis, comprising an extract of Quecia Undulata or a fraction thereof as an active ingredient.

Technical Field

 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.

Background Art

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. At this time, 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 (lame lUpoda, Filapoda) 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. The limitation of this surgical procedure is that the 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. Thus, it is a possibility that angiogenesis inhibitors can be commonly used in all sol id tumors. Second, 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. In addition, 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. Third, since 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. Lastly, in the conventional anticancer drug delivery method, 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.

In the early 1970's, Dr. Folkman of Harvard Medical School proposed the hypothesis that cancer cells secrete specific factors to induce angiogenesis. It has been shown to play an important role in the metastasis of cancer cells and the presence of factors that inhibit allergic angiogenesis (J. Folkman, et al., Science, 1987, 235: 442). In 1985 angiogenin, an angiogenic inducer, was first discovered by secretion of human crystalline cancer cells by a team of Dr. Vallee of Harvard Medical School. In addition, sol id tumors can continue to grow by nourishing and excreting waste products using new blood vessels induced around them, and these cancer cells are connected to the circulation and spread to other parts of the lungs, liver, etc. (1. A. liotta, et al., Cell, 1991, 64: 327). In addition, 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). These facts show that, in the early stages of cancer research, cancer cells were understood as anaerobic respiratory tissues, and oxygen and nutrient supply were absolute for cancer cell growth. In 1993, German scientists announced that chemicals that inhibit the induction of angiogenesis were isolated from soybeans (T. Fotsis, et al., Proc. Natl. Acad. Sci. USA, 1993, 90: 2690). 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. Reported disappearance (FM Uckun, et al., Science, 1995, 267: 886). therefore. The discovery of new angiogenesis inhibitors is a clue to the mechanism of cancer growth, and can be applied to early diagnosis, prevention and treatment of cancer, as well as diabetic retinopathy, a disease related to angiogenesis. It can also be widely used to treat diseases such as rheumatoid arthritis, chronic inflammation and hemangiomas. For this reason, academia and industry have continued to pay attention to it and to make efforts for research and development (W. Auerbach, et al., Pharmac. Ther., 1994, 61: 265). Accordingly, 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.

[Detailed Description of the Invention] [Technical problem]

 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.

Technical Solution

 In order to achieve the above object, 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.

 In addition, 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.

 In addition, 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.

 In another aspect, the present invention provides a health food for inhibiting neovascularization containing Quecia Undulata extract or a fraction thereof as an active ingredient.

 In addition, 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.

Advantageous Effects

 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.

【Brief Description of Drawings Γ

 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 卜 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.

 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.

[Best form for implementation of the invention]

 Hereinafter, terms used in the present invention are defined. The term "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.

 The term "prevention", as used herein, means any action that inhibits cancer formation or delays the onset by administration of a composition of the present invention.

 As used herein, the terms "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. As used herein, the term "administration" means providing a patient with a given composition of the present invention in any suitable manner.

 As used herein, 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.

As used herein, 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. Hereinafter, 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.

 1) extracting by adding an extraction solvent to Quecia Undulata;

 2) cooling the extract of step 1) and then filtering; And

 3) drying the filtered extract of step 2) under reduced pressure.

In the above method, 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.

 As a method of extracting the Quessa Undulata extract, 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. 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 3 to 5 times. The extraction temperature may be 20 to 40, but is not limited thereto. In addition, the extraction time may be 12 to 48 hours, but is not limited thereto.

 In the above method, the decompression concentration in step 3) may be to use a vacuum decompression concentrator or a vacuum rotary evaporator, but is not limited thereto. In addition, 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. Provided is 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.

 1) extracting by adding an extraction solvent to queciaundulata;

 2) cooling the extract of step 1) and then filtering; And

 3) drying the filtered extract of step 2) under reduced pressure.

In the above method, 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. In addition, the extraction time may be 12 to 48 hours However, it is not limited thereto.

 In the above method, the decompression concentration in step 3) may be to use a vacuum decompression concentrator or a vacuum rotary evaporator, but is not limited thereto. In addition, 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.

 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. In order to find out the effect of Quecia Undulata extract on cell migration, 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 卜 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). In addition, modified Boyden chambers were used to determine the effect of the Quescia Undulata fraction on cell migration. Fraction 1 (methanol and water 1: 1 elution fraction) of Quescia Undulata and Fraction 2 (Quecia Undulata) of the present invention using a cell migration assay that allows cell migration to be identified microscopically using a boyden chamber. And water 2: 1 elution fraction) were measured for the degree of cell migration inhibition of colorectal cancer cell lines DlD-1 (PRl-3), D1D-1, myeloma cell line A375P, prostate cancer cell line DU145, and pancreatic cancer cell line Miapaca2. As a result, it was confirmed that the migration of cancer cells by more than 80% at a concentration of 5 ug / ml of Quecia Undulata fraction (see Figure 2). In addition, in order to determine the effect on the cell migration according to the concentration of the Quescia Undulata fraction, the Quebec of the present invention using a cell migration assay that can confirm the cell movement under a microscope using a modified Boyden chamber. 200 ug / ml of colorectal cancer cell line D1D-UPR 卜 3 for fraction 1 (methanol and water 1: 1 elution fraction) of undulata and fraction 2 (methanol and water 2: 1 elution fraction) of Quecia , 500 ug / ml, lug / ml, 2 ug / ml and 5 ug / ml treatment was measured for cell migration inhibition. As a result, cell migration inhibition was confirmed in a concentration-dependent manner of fraction 1 or fraction 2 of Quecia Undulata (see FIG. 3). 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. An 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). Thus, 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. . Or 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, its active fraction or a combination thereof. It 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. As the 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. As the 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. However, 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.

As a result of toxicity experiments by orally administering the composition of the present invention to rats, 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. ᅳ Also, 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.

 In addition, Quecia Undulata (Quassia undulata) provides a health food for inhibiting neovascular formation containing an extract or a fraction thereof as an active ingredient.

 In addition, it 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 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.

When using the Quescia Undulata extract of the present invention, 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). Generally, in the preparation of food or beverages, 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. However, in the case of long-term intake for health and hygiene or health control, 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. . There is no particular limitation on the kind of food. Examples of 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, ¾, 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. As the 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.

In addition to the above, the Quescia Undulata extract 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.

Since 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, For the treatment containing Rata root extract or fractions thereof as an active ingredient It may be usefully used as a pharmaceutical composition. 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.

 Since 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.

 Since 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. Hereinafter, 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 Preparation of Quecia Undulata Root Extract

 <1-1> Preparation of Methanol Extract of Quecia Undulata Root

Dried Quescia Undulata Root to Supply from US Botanical liaisons 11C received. 1 kg was pulverized, immersed in methanol 4 1, and allowed to stand at room temperature for 5 days. The extract was filtered and concentrated under reduced pressure to give 60 g of methanol extract of Quecia Undulata root.

<1-2> Preparation of Ethanol Extract of Quecia Undulata

 1 kg of dried Quescia Undulata roots were crushed and immersed in ethanol 4 1. It was left at room temperature for 5 days. The extract was filtered and concentrated under reduced pressure to obtain 60 g of an extract of ethane of Quecia Undulata root.

<1-3> Preparation of hydrothermal extract of Quecia Undulata

 1 kg of dried Quescia Undulata roots were ground and immersed in water 4 1 and left at room temperature for 5 days. The extract was filtered and concentrated under reduced pressure to obtain 80 g of hydrothermal extract of Quecia Undulata root.

Example 2 Preparation of Active Fraction of Quecia Undulata Extract

 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).

Example 1 Analysis of Cell Migration Inhibition of Quecia Undulata Extract and Fractions thereof

 Quebec Undulata root extract and fractions thereof extracted in <Example 1> and <Example 2> using the modified Boyden chamber (Modified Boyden chamber) to confirm the cell migration inhibition in rectal cancer cells It was measured using a cell migration assay that can be confirmed by a microscope.

Specifically, the modified Boyden chamber (Neuro Probe) and 8 μπι pore-sized membrane (membrane, neuro probe) and staining solution required for cell staining Kimja stain (Giemsa solution, Sigma) was prepared. 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. Cells overexpressing the PR1-3 (Phosphatase of regenerating liver-3) gene, which plays an important role in cancer cell migration and metastasis, in the colon cancer cell line DID-1 (purchased from ATCC, USA) Removed with trypsin / EDTA, treated with Soybean trypsin inhibitor, washed three times with serum-free medium to prepare the cells to 4 X 10 ⁵ cells / m £. At the bottom of the modified Boyden chamber, extracts of Quecia Undulata, or fractions thereof, were placed in chamber wells with 30% each of 10% FBS, and placed in 8 μι pore-sized membranes. On top of it a silicon gasket was covered, a top plate was placed over the gasket and tightened with a nut. 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. A little nail polish was applied to the edge of the cover slip and it was fixed on the slide glass. This prepared sample was observed by using an inverted microscope the number of cells moved. In the above method, cancer cells and smooth muscle cell migration inhibition by the compound of the present invention and its derivatives were observed and measured, and cell migration inhibition was calculated by the following formula.

[Equation 1] ¾ 훽 해 ■

그 결과, 퀘시아 운둘라타 추출물 10 ug/ml에서 90% 이상의 대장암 세포주 (D1D-1)의 세포이동 저해활성을 확인하였다 (도 1).

As a result, the cell migration inhibitory activity of more than 90% colorectal cancer cell line (D1D-1) was confirmed in 10 ug / ml of Quecia Undulata extract (FIG. 1).

 In addition, at a concentration of 5 ug / ml of the Quecia Undulata fraction, cancer cell migration of colorectal cancer cell lines D1D-KPR1-3), D1D-1, myeloma cell line A375P, prostate cancer cell line DU145, and pancreatic cancer cell line Miapaca2 was not less than 80%. It was confirmed to inhibit (FIG. 2).

 In addition, fraction 1 of the Quescia Undulata (methane and water 1: 1 elution fraction) and Quescia Undulata (fraction fraction 2) of the Quecia Undulata (methane and water 2: 1 eluted fraction) were observed in colon cancer cell line D1D-KPR1-3. Concentration-dependent cell migration inhibition was confirmed (FIG. 3).

Experimental Example 2 Quesia Undulata Root Extract and Fractions thereof Determination of Angiogenesis Inhibitory Activity

 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.

Specifically, in vivo endothelial cell morphogenesis analysis was used to inhibit angiogenesis of MIG1 and its derivatives as vascular endothelial cells (HUVECsXATCC, USA). 24-well 1 cell culture plates and matrigel matrix (D biosciences) were prepared for the experiment. As a necessary equipment, an inverted microscope equipped with a digital camera (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. 24-well cell culture folate Coated with 0.2 Matrigel matrix per well and incubated for 1 hour in a 37 ⁰ C incubator. Add 0.20 of 20000 cells prepared per well and add C0 ₂ for 30 minutes. It was incubated in the incubator. Then, fresh medium in which MIG1 and active fraction 2 of <Example 2> were diluted by concentration was added to each well, and 1% serum was added thereto, followed by incubation for 24 hours. At this time, vascular endothelial cells (HUVECs) were formed using an inverted microscope for the degree of inhibition of tube formation in forming a tube shape.

 As a result, it was confirmed that the treatment with Quebec Undulata active fraction 2 at a concentration of 5 ug / ml has an anti-angiogenic activity because it was excellent in tube formation (FIG. 4). Preparation Example 1 Preparation of Pharmaceutical Formulation

 <1-1> Preparation of powder

 Quecia Undulata Root Extract of Example <1-1> 0.1 g Lactose 1.5 g Talc 0.5 g The above ingredients were mixed and filled in an airtight cloth to prepare a powder.

<1-2> Preparation of the tablet

 Quecia Undulata Root Extract of Example <1-1> 0.1 g Lactose 7.9 g Crystalline Chlorose 1.5 g Magnesium Stearate 0.5 g After mixing the above components, a tablet was prepared by a direct tableting method. It was. <1-3> Preparation of the capsule

Quecia Undulata Root Extract of Example <1-1> 0.1 g Lactose 7.9 g Crystalline Salose 1.5 g Magnesium Stearate 0.5 g Mixture of the above components: Tablets were prepared by a direct _tableting method ( _Hal - _fuh ¾ ¾). <1-3> Preparation of the capsule

 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 ¾ capsule To prepare a capsule by filling into a hard capsule according to.

<1-4> Preparation of Injection _.

 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.

<1-5> Preparation of Liquid

<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

 <2-1> Preparation of flour food

 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.

<2-2> Preparation of Soup and Gravy

 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.

<2-3> Preparation of ground beef

 10 parts by weight of Quecia Undulata Root Hydrothermal Extract of Example <1-3> was added to the ground beef to prepare a ground beef for health promotion.

<2-4> Manufacture of dairy products

 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.

<2-5> Preparation of wire

 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.

 Cereals (30 parts brown rice, 15 parts barley, 20 parts barley) ，

 Seeds (7 parts by weight perilla, 8 parts by weight black beans, 7 parts by weight black sesame seeds),

 Quecia Undulata Root Hydrothermal Extract of Example <1-3> (3 parts by weight), Ganoderma lucidum (0.5 parts by weight),

 Foxglove (0.5 part by weight)

<2-6> Preparation of health supplement food

Quecia Undulata Root Hot Water Extract of Example <1-3> 100 nig Vitamin Mixture Vitamin A Acetate 70 Vitamin E 1.0 nig Vitamin B1 0.13 mg Vitamin B2 0.15 nig Vitamin B6 0.5 nig Vitamin B12 0.2 g Vitamin C 10 nig Biotin 10 ug Nicotinamide 1.7 nig Folic acid 50 ug Calcium Pantothenate 0.5 mg Mineral Mixture Ferric Sulfate 1.75 mg Zinc Oxide 0.82 nig Magnesium Carbonate 25.3 mg Potassium Phosphate 15 nig Calcium Diphosphate 55 nig Potassium Citrate 90 nig Carbonate 100 grams Magnesium Chloride 24.8 mg The composition ratio of the vitamin and mineral mixtures described above is a relatively suitable composition for health foods, but the composition ratio may be arbitrarily modified. After mixing the above ingredients according to the food manufacturing method; to prepare a granule, it can be used in the manufacture of health food composition according to the usual method.

Production Example 3 Production of Healthy Drinks

Quencia Undulata Root Extract of Example <1-3> 100 mg citric acid 100 mg oligosaccharide 100 mg plum concentrate 2 nig taurine 100 mg Purified water was added to the mixture according to the above 500 \ ni normal health beverage manufacturing method Next, after stirring and heating at 85 ⁰ C for about 1 hour, the resulting solution is filtered to obtain a sterilized 1 1 container, sealed and sterilized and then stored for storage before use in the manufacture of the beverage composition of the present invention.

 Although the 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.

Industrial Applicability As described above, 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.

Claims

[Range of request]  [Claim 1]  A pharmaceutical composition for inhibiting cancer or cancer metastasis, comprising an extract of Quecia Undulata (ft / ass / a undulata) or a fraction thereof as an active ingredient. [Claim 2]  According to claim 1, wherein the extract is a pharmaceutical composition for inhibiting cancer or cancer metastasis, characterized in that extracted from the root of Quecia Undulata. [Claim 3] The pharmaceutical composition for inhibiting cancer or cancer metastasis according to claim 1, wherein the extract is extracted using water, lower alcohols of C ₂ or a mixture thereof as a solvent. [Claim 4]  4. The pharmaceutical composition for inhibiting cancer or cancer metastasis according to claim 3, wherein the lower alcohol is methanol or ethane. [Claim 5]  The pharmaceutical composition for inhibiting cancer or cancer metastasis according to claim 1, wherein the fraction is an active fraction further extracted with 50% to 100% methane extract of Quercia undulata methanol. [Claim 6] The method of claim 1, wherein the cancer is selected from the group consisting of colon cancer, gastric cancer, prostate cancer, breast cancer, kidney cancer, liver cancer, brain tumor, lung cancer, uterine cancer, colon cancer, bladder cancer, and pancreatic cancer. Pharmaceutical composition for. [Claim 7]  Pharmaceutical composition for inhibiting neovascularization, containing Quecia Undulata extract or a fraction thereof as an active ingredient ᅳ [Claim 8]  Pharmaceutical composition for the prevention and treatment of diseases caused by neovascularization containing Quecia Undulata extract or fractions thereof as an active ingredient. [Claim 9]  The method of claim 8, wherein the disease caused by neovascularization is selected from the group consisting of diabetic retinopathy, rheumatoid arthritis, chronic inflammation, and hemangioma. Composition. [Claim 10]  Health food for inhibiting cancer or cancer metastasis containing Quecia Undulata extract or fractions thereof as an active ingredient. [Claim 11]  11. The cancer or cancer metastasis suppressor according to claim 10, wherein the cancer is 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 and pancreatic cancer. Dragon health food. - [Claim 12]  Health foods for inhibiting neovascularization, containing Quesaa undulata extract or fractions thereof as an active ingredient. Claim 131 Quebec Undulata extract or fractions thereof as an active ingredient Health foods for the prevention and improvement of diseases caused by neovascularization. [Claim 14]  14. The health for preventing and improving diseases caused by neovascularization according to claim 13, wherein the disease due to neovascularization is selected from the group consisting of diabetic retinopathy, rheumatoid arthritis, chronic inflammation and angioma. food. [Claim 15]  A method of treating cancer, comprising administering a pharmaceutically effective amount of Quescia Undulata extract or a fraction thereof to a subject with cancer. [Claim 16]  A method of inhibiting cancer metastasis, comprising administering a pharmaceutically effective amount of Quescia Undulata extract or a fraction thereof to a subject with cancer. [Claim 17]  A method of preventing cancer, comprising administering to a subject a pharmaceutically effective amount of Wessia undulata extract or a fraction thereof. [Claim 18]  A method of inhibiting angiogenesis, comprising administering to a subject a pharmaceutically effective amount of Wessia undulata extract or a fraction thereof. [Claim 19]  Use of a Quexia Undulata extract or a fraction thereof for use as a pharmaceutical composition for the prevention and treatment of cancer. [Claim 20] Use of Quecia Undulata extract or fractions thereof for use as a health food for cancer prevention and improvement. [Claim 21]  Use of Quecia Undulata extract or fractions thereof for use as a health food for inhibiting angiogenesis.