WO2012108744A2 - Composition and health functional food for treating brain cancer comprising inula flower extract - Google Patents

Abstract

The present invention relates to a novel use of inula flower extract, and more specifically, relates to a composition for preventing and treating brain cancer, the composition comprising inula flower ethanol extract as an active ingredient, and to functional food for preventing brain cancer, the functional food comprising the inula flower ethanol extract, which includes a sitologically acceptable food supplement additive, as an active ingredient. The composition and functional food for treating brain cancer according to the present invention are effective in inhibiting growth and inducing death of cancer cells, and thereby, can be effectively used in treating and preventing brain cancer.

Description

Brain cancer composition and health functional food comprising the extract

The present invention relates to a novel use of the mussel extract. Specifically, the present invention relates to a therapeutic composition and a functional food containing a capillary extract as an active ingredient exhibiting excellent prophylactic or therapeutic efficacy against brain cancer.

Among the major diseases of modern people, researches on the treatment and diagnosis of cancer are being conducted mainly on lung cancer, liver cancer, and stomach cancer, which have high incidence. However, studies on brain cancer, esophageal cancer, colon cancer, pancreatic cancer, etc., which have a low incidence, are relatively poor. Clinical symptoms of brain cancer include headache, epileptic seizures, vomiting, motor paralysis, overlapping objects, poor vision, hormonal abnormalities, hearing loss, dizziness, and speech disorders.

"Brain cancer" refers to abnormally increased proliferation of any type of neuron, also referred to as primary brain cancer, or any other cancer that metastasizes to the central nervous system (CNS), also referred to as brain metastasis. For example, most neurons that are cells found in or containing the CNS, including neurons, microglia, and astroglia, are "finally differentiated", meaning that they no longer have the ability to complete the cell cycle. Kornblith et al, (1986), Cancer: Principles and Practice of Oncology, 2nd Ed., DeVita, V., Hellman, S., Rosenberg, S, eds., JB Lippincott Company, Philadelphia, Chapter 41: Neoplasms of the Central Nervous System). Even if neurons enter the cell cycle, they are usually unable to complete the process because they are apoptotic (cell death) (Multani, A.S., et al, Neoplasia 2 (4), 339-45 (2000)). Primary brain cancer can only occur in those cases where the nerve cells lose their protective ability to undergo apoptosis. Examples of primary brain cancers include, but are not limited to, neuroma, astrocytoma, neuroblastoma, glioma, meningioma, oligodendrocyte, stromal blastoma, spinal cord tumor and neuromyoma.

Gliomas comprise about 60% of all primary CNS tumors and typically occur in the cerebral hemispheres of the brain, but can be found in other areas such as the visual nerve, brain stem or cerebellum. Gliomas can be classified into groups according to the type of glial cell from which they originated (Kornblith et al, (1986), Cancer: Principles and Practice of Oncology, 2nd Ed., DeVita, V., Hellman, S., Rosenberg , S, eds., JB Lippincott Company, Philadelphia, Chapter 41: Neoplasms of the Central Nervous System). The most common type of glioma is astrocytoma. These tumors develop from star-shaped glial cells called astroglia. Astrocytes are assigned a rating according to their malignancy. Low-grade astrocytomas, also known as grade I and II astrocytomas, are minimal malignant, grow relatively slowly, and can often be completely eliminated using surgery. Mid-grade astrocytoma, also known as grade III astrocytoma, grows faster and is more malignant. Grade III astrocytoma is treated with radiation and some chemotherapy following surgery. High-grade astrocytoma, also known as grade IV astrocytoma, grows rapidly, invades nearby tissues and is very malignant. Grade IV astrocytomas are usually treated with a combination of radiation and chemotherapy following surgery. Glioblastoma multiforme is a grade IV astrocytoma, which is the most malignant and lethal primary brain tumor (Id). When the same surgical techniques and principles are applied to treat glioblastoma multiforme and less malignant brain tumors, complete elimination of glioblastoma multiforme tumors is more difficult to achieve.

Malignant differences are also reflected in the prognosis for patients with primary brain tumors. Patients treated for grade I astrocytomas typically can survive for more than 10 years without recurrence, while the average survival for patients with grade IV astrocytoma tumors is 15 weeks after surgical treatment. Because of the high-malignant growth potential of grade IV astrocytoma tumors, only 5% of patients survive for 1 year after surgery alone and have nearly 0% survival after 2 years. Radiation therapy combined with surgical treatment increases survival by about 10% after two years of treatment, but virtually no patients survive for more than five years.

While therapies of surgery, radiation therapy and chemotherapy provide an opportunity for a moderately increased lifespan for patients with grade IV astrocytoma brain tumors, there are many risks associated with each treatment method. The benefit of treatment is minimal, and treatment can significantly reduce the quality of the patient's short-lived life. Thus, in particular, since CNS tumors represent the most common group of solid tumors in young patients, there is a clear need in the art for primary brain cancer prevention and treatment methods that overcome the disadvantages of the above-mentioned conventional approaches. Brain tumors are a secondary-induced cause of cancer-related death in infants, with approximately 25% of all such deaths, with current therapies in which most of these infants die within the first year of diagnosis.

Compared with primary brain tumors, the number of occurrences of brain metastases is much higher. Approximately 100,000 patients have symptomatic intracranial metastases in the United States each year, and one quarter of cancer patients have tumor metastasis according to autopsy studies (Newton, HB, et al, J. Neurooncol. 61, 35-44 ( 2003). Brain metastasis results from primary tumors elsewhere in the body, including, but not limited to, lung cancer (both small and non-small cell), breast cancer, colorectal cancer, prostate cancer, melanoma and pancreatic cancer. Particularly in patients with metastatic breast cancer, the incidence of brain metastasis is diagnosed at a rate of 10-20% (Tyson, R.M. et al, Therapy 3 (1), 97-112 (2006)). Breast cancer is the second leading cause of cancer-related death in women, and nearly all deaths from breast cancer are due to metastatic disease with brain metastases found in 30% of patients at autopsy.

Standard modes of treatment include surgical resection, chemotherapy and radiation therapy, in particular whole-brain radiation therapy (WBRT) and stereotactic radiosurgery or combinations thereof. Surgery for brain metastases can improve survival, especially in patients with a single lesion. Surgery, however, may not be possible in terms of multiple lesions, lesions that are difficult to surgically approach, or inability to withstand surgery. In breast cancer, 50% of patients with brain cancer metastases have multiple metastases, making them less suitable as surgical candidates. WBRT can improve intermediate survival over untreated and as an adjuvant for surgery, which reduces the chance of relapse and dying nerve death, but does not change survival or level of action. SRS provides a method for treating brain metastases that cannot be surgically resected by location or patient symptoms. SRS provides an improvement in quality of life but does not provide survival benefits, except for patients with a single metastasis. The use of chemotherapy in the treatment of brain metastases is hampered by the impossibility of high molecular weight compounds, limiting most chemotherapeutic agents across the blood brain barrier. This is reflected in the fact that chemosensitive tumors, such as most metastatic breast carcinomas, often exhibit a complete systemic response to chemotherapy simultaneously with tumor progression in the brain. However, this initial resistance to the use of chemotherapy in the treatment of brain metastases has recently changed based on observations in animal models and human brain tumor autopsies, and metastatic lesions cause blood brain barrier insufficiency, whereby chemotherapy Drugs can always enter the tumor. Radiation therapy combined with chemotherapy has evolved from a first-line approach in the treatment of brain metastases.

However, there are serious risks and limitations associated with all current methods of treatment. Radiotherapy in attempts to deliver highly destructive doses of ionizing radiation, often through normal tissues of the body, preferably to highly specific and often incompletely defined areas of cancerous tissue, is the first of its kind to cause memory loss and personality deformation. Because of the disruption of the normal nervous system or other tissues it is severe and can have significant side effects. Chemotherapy in attempts to kill cancer cells in place of normal cells, preferably through the administration of other types of chemical agents or drugs in the tissues of the body, is limited in efficacy by the currently available chemical agents and is not intended to be toxic and inadequate. May cause side effects. Surgery in an attempt to mechanically disrupt or hinder the progression of cancer can also cause serious side effects or consequences as a result of mechanical trauma or destruction of normal tissue. Some problems associated with the above approaches include (i) deleterious side effects, including alteration of intelligence, learning ability, memory, motor skills, consciousness and emotions; (ii) recurrence of tumors within 3 to 5 years of treatment because of the development of resistance to these therapies; (iii) death due to ineffectiveness of this treatment. From the foregoing, it will be apparent that there is an urgent need to develop a chemotherapeutic agent that can cross the blood brain barrier in an effective amount to reduce neoplastic expansion and / or growth of cancer in the central nervous system, which is not yet satisfied.

Brain cancer is a generic term for primary brain cancer that develops in the brain tissue and the envelope that surrounds the brain, and secondary brain cancer that has metastasized from cancer that occurs in the skull or other parts of the body. Such brain cancers are often distinguished from cancers occurring in other organs. First, lung, stomach, and breast cancers occur in one or two types of organs, and their properties are the same and similar. However, the brain develops a wide variety of cancers. For example, glioblastoma multiforme, malignant gliomas, lymphomas, germ cell tumors, metastatic tumors, and the like.

Among these, glioma, especially glioblastoma multiforme (GBM), is the most malignant and aggressive disease, and has a very poor prognosis. The average survival time after diagnosis is very deadly. Since the boundary between brain cells and tumor cells is not clear, it is almost impossible to completely remove the GBM surgically.

Therefore, while the development of chemical therapeutics other than surgical treatment is urgently needed, effective treatments have not been developed yet, and research and development thereof are required.

Inulae Flos is a flower of the perennial Inula Japonica Thunb. The diameter is 10-15 mm and has a spherical shape. It is composed of several guns and arranged in a tile shape. It has an unusual smell, tastes sweet and bitter behind. In the ground part of the fireweed, Xanthanolide, inulicin, deacetylinulicine, bigelovin, ergolide, Sesquiterpene lactone 2,3-dihydroaromaticin, and flavonoid-based patulintin 7-Ο- (6 ''-isobutyryl) glucoside [patuletin 7-Ο- (6 ''- isobutyryl) glucoside], isoraminetin 3-glucoside, patulitrin, etc. (Information and Shin Min-kyo), Dohae Hyangje (Drug), Daelim, Yeonglimsa, pp 1054-1056, 1998 ). Antidiabetic effects have been reported in scientific studies on capillary extracts (Shan JJ, et al., Anti-diabetic and hypolipidemic effects of aqueous-extract from the flower of Inula japonica in alloxan-induced diabetic mice, Biol. Pharm , Bull., 29, pp 455-459, 2006),

However, it is not known about the anticancer effect of brain cancer.

Accordingly, the present inventors completed the present invention by confirming that the extracts can effectively kill brain cancer cells during the study of the herbal medicines for the recovery.

It is an object of the present invention to provide a composition and functional food for the treatment of brain cancer containing the abalone extract as an active ingredient.

In order to achieve the above object, the present invention provides a composition for the prevention and treatment of brain cancer comprising an active ingredient extracted from the organic solvent. The organic solvent is preferably ethanol.

In another aspect, the present invention provides a functional food for preventing brain cancer containing a ethanol extract of the above-mentioned containing a food supplement acceptable food supplement as an active ingredient.

Hereinafter, the present invention will be described in detail.

The present invention provides a composition for the prevention and treatment of brain cancer containing Inulae Flos ethanol extract as an active ingredient. The composition of the present invention comprises a capsular extract as an active ingredient, and may further include a pharmaceutically acceptable carrier or diluent.

In the composition for preventing and treating brain cancer of the present invention, the ethanol extract is preferably extracted for 24 hours at 50 ℃, wherein the ethanol extract is more preferably dried and concentrated at 45 ℃ reduced pressure conditions, the ethanol is Most preferred is 95%.

In addition, in the composition for the prevention and treatment of brain cancer of the present invention, the composition is selected from the primary brain cancer crowd consisting of neuroma, astrocytoma, neuroblastoma, glioma, meningioma, rare oligodendrocyte, stromal blastoma, spinal cord tumor and neuromyoma It is preferably applied to brain cancer.

In addition, in the composition for preventing and treating brain cancer of the present invention, the composition preferably comprises a pharmaceutically acceptable carrier or diluent.

The "pharmaceutically acceptable carrier" is a pharmaceutically acceptable substance such as a liquid or solid filler, diluent, excipient or solvent which serves to transport the active ingredient from one organ or part of the body to another organ or part of the body. , Composition or vehicle.

The composition for treating brain cancer of the present invention may be prepared as a medicament by adding one or more pharmaceutically acceptable carriers together with the active ingredient. The carrier may include, but is not limited to, saline, buffered saline, water, glycerol and ethanol, and any suitable agent known in the art (Remingtons's Pharmaceutical Science (Recent Edition), Mack Publishing Company, Easton PA) may be used. .

Formulations for pharmacizing the extract of the present invention can be administered orally during clinical administration and can be used in the form of general pharmaceutical formulations, when formulated, commonly used fillers, extenders, binders, wetting agents, disintegrants And diluents such as surfactants or excipients. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and liquid preparations for oral use include suspensions, solvents, emulsions, and syrups. In addition to liquids and paraffins, various excipients may be included, such as wetting sweeteners, fragrances, preservatives and the like.

The composition of the present invention may be administered in various parenteral formulations during actual clinical administration, and solid preparations include tablets, pills, powders, granules, capsules, and the like. In addition to water, liquid, and paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. Specifically, preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, 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, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used. In addition, calcium or vitamin D ₃ may be added to enhance the efficacy of the treatment. Such compositions may be presented in unit-dose (single) or multi-dose (several) containers, such as sealed ampoules and vials, and immediately before use, sterile liquid carriers such as injectable water. Can be stored under freeze-drying conditions requiring only the addition of. Immediate injection solutions and suspensions can be prepared from sterile powders, granules and tablets.

The formulations of the present invention can be applied differently depending on the age, sex, condition of the subject, the absorption of the active ingredient in the body, the inactivation rate and excretion rate, the drug used in combination. The invention also includes formulations of dosage units. The formulations are present in individual dosage forms, such as tablets, coated tablets, capsules, pills, suppositories, and ampoules, wherein the amount of active compound in the drug corresponds to the fraction or multiple of the individual dosage. Dosage units may contain, for example, one, two, three or four times the individual dosage, or 1/2, 1/3 or 1/4 times. The individual dosages preferably contain an amount in which the active compound is administered at one time, which usually corresponds to all, 1/2, 1/3 or 1/4 times the daily dosage.

As used herein, the term "extract" refers to an active ingredient isolated from natural products. The extract may be obtained by an extraction process using water, an organic solvent, or a mixed solvent thereof, and includes an extract, a dry powder thereof, or any form formulated using the same.

In a specific embodiment of the present invention, the ethanol extract of the ablation killed 73.4% of U-87 MG brain cancer cells at 100 μg / ml and the EC ₅₀ (half maximal effective concentration) was 25.132 μg / ml. The above results demonstrate that the mussel extract of the present invention has excellent killing activity of U-87 MG cells and further has brain cancer treatment and prophylactic activity.

As used herein, the term "prevention" means any action that inhibits or delays the onset of brain cancer by administration of the composition.

As used herein, the term "treatment" means any action that improves or advantageously alters the symptoms of brain cancer by administration of the composition.

The sundae extract in the present invention can be extracted and used using water, an organic solvent, or a mixed solvent thereof. Preferably it is extracted using an organic solvent, in particular ethanol. The extracted solution can be used directly or can be concentrated and / or dried. When extracted with an organic solvent, methanol, ethanol, isopropanol, butanol, ethylene, acetone, hexane, ether, chloroform, ethyl acetate, butyl acetate, dichloromethane, N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), 1,3-butylene glycol, propylene glycol, or a mixed solvent thereof may be used and extracted by room temperature or warming under conditions where the active ingredient of the herbal medicine is not destroyed or minimized. Depending on the organic solvent to be extracted, the degree of extraction and loss of the active ingredient of the drug may vary, so select an appropriate organic solvent. The extraction method is not particularly limited, and examples thereof include cold needle extraction, ultrasonic extraction, reflux cooling extraction, and the like. Filtration is a process of removing the suspended solid particles from the extract, it may be used to filter the particles using cotton, nylon or the like, or may be used, such as ultrafiltration, cryofiltration, centrifugal separation, but is not limited thereto.

Concentration of the extract may be used, such as concentrated under reduced pressure, reverse osmosis concentration. The drying step after concentration includes freeze drying, vacuum drying, hot air drying, spray drying, reduced pressure drying, foam drying, high frequency drying, infrared drying, and the like. If desired, a process of grinding the final dried extract may be added.

In addition, the extract can perform an additional fractionation process. Preferably, the extract is suspended in distilled water to obtain a nonpolar solvent soluble layer by extraction and separation with a nonpolar organic solvent such as hexane, ether, dichloromethane, chloroform, ethyl acetate, or a mixed solvent thereof. It can be used by concentrating and / or drying it.

In the present invention, the term "pharmaceutically acceptable salts" means salts derived from pharmacologically or physiologically acceptable inorganic acids, organic acids and bases. Examples of suitable acid include hydrochloric acid, bromic acid, sulfuric acid, nitric acid, perchloric acid, fumaric acid, maleic acid, phosphoric acid, glycolic acid, lactic acid, salicylic acid, succinic acid, toluene-p-sulfonic acid, tartaric acid, acetic acid, citric acid, methanesulfonic acid, Formic acid, benzoic acid, malonic acid, naphthalene-2-sulfonic acid, benzenesulfonic acid, and the like. Salts derived from suitable bases may include alkali metals such as sodium, alkaline earth metals such as magnesium, ammonium and the like.

The pharmaceutical composition for preventing and treating brain cancer diseases of the present invention comprises 0.1 to 50% by weight of the extract or compound based on the total weight of the composition. In addition, the composition does not increase the efficacy, but may include additional ingredients that are commonly used in the pharmaceutical composition to improve the smell, taste, time and the like. In addition, the composition adds inorganic and organic additives such as vitamins B1, B2, B6, C, E, niacin, carnitine, betaine, folate pantothenic acid, biotin, zinc, iron, calcium, chromium, magnesium, and mixtures thereof. It can be included as. In addition, the composition may include a substance having a therapeutic activity against brain cancer used alone or used in the past.

As used herein, the term "patient" refers to humans and horses, sheep, pigs, goats, camels, who have a disease caused by brain cancer and its direct and indirect causes, and whose symptoms can be improved by administering the composition of the present invention. Means antelope, dog and other animals. By administering to the patient a composition comprising the extract of the present invention, the above-mentioned brain cancer can be effectively prevented and treated. The composition of the present invention can be administered in parallel with existing brain cancer therapeutics.

As used herein, the term "administration" means introducing a predetermined substance into a patient by any suitable method, and the route of administration of the composition of the present invention is oral or parenteral via any general route as long as the target tissue can be reached. May be administered. In addition, the composition may be administered by any device in which the active agent may migrate to the target cell.

The composition of the present invention is administered in a pharmaceutically effective amount. As used herein, the term “pharmaceutically effective amount” means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and an effective dose level refers to the sexually transmitted disease, age, severity, and drug activity of the patient. , Drug sensitivity, time of administration, route of administration and rate of release, duration of treatment, factors including concurrently used drugs, and other factors well known in the medical arts. The compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents and may be administered sequentially or simultaneously with conventional therapeutic agents. It may be single or multiple doses. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect in a minimum amount without side effects, and can be easily determined by those skilled in the art. The method of administering the composition comprising the extract or compound prepared according to the preparation method of the present invention is preferably oral administration or intravenous administration. In general, when the effective dose is oral administration, it is usually 1 to 1 time per adult. 500 mg / kg is preferred, and in the case of intravenous administration, 1 to 100 mg / kg is preferred, and may be administered 2-3 times a day. Dosage levels for a particular patient may vary depending on sex, age, health condition, diet, time of administration, method of administration, drug mixture, the condition of the patient, and the extent of the onset of neurological disease.

In another aspect, the present invention provides a functional food for preventing brain cancer containing an Inulae Flos ethanol extract containing a food supplement acceptable additive as an active ingredient.

Functional food of the present invention preferably contains 0.1 to 5% by weight, more preferably 1% by weight of the ethanol extract relative to the total weight.

In the present invention, as a result of introducing the capillary extract of the present invention into U-87 MG brain cancer cells, it was confirmed that U-87 MG brain cancer cells are killed (see FIG. 1 ). Therefore, it can be seen newly that the extract of the sun has a brain cancer treatment effect. Thus, in the present invention, the present invention was completed by preparing a functional food for preventing brain cancer containing the abalone extract as an active ingredient (see Preparation Example 2 ).

As discussed above, the mucus extract of the present invention inhibits the growth of brain cancer cells and induces apoptosis. Therefore, the composition for treating brain cancer according to the present invention will be very effective in the treatment of brain cancer patients.

1 is a result of the Alamar Blue analysis to determine the effect of the introduction of acupuncture on the growth of brain cancer cells in human brain cancer U-87 MG cells. The horizontal axis of the figure shows the concentration of the extract, the vertical axis shows the survival rate of brain cancer cells.

2 is a result of Alamar Blue analysis to determine the effect of the introduction of turmeric extract on the growth of brain cancer cells in human brain cancer U-87 MG cells. The horizontal axis of the figure shows the concentration of the extract, the vertical axis shows the survival rate of brain cancer cells.

Hereinafter, the present invention will be described in more detail based on the following examples. However, the following examples are only for illustrating the present invention, and the present invention is not limited to the following examples and may be changed to other embodiments equivalent to substitutions and equivalents without departing from the technical spirit of the present invention. Will be apparent to those of ordinary skill in the art.

<Example 1> Preparation of the sundae extract

3 kg of Seonhwa (Chinese) purchased from Seoul medicinal herb were dried and ground for 5 days at the shade and room temperature. The ground trituration was immersed in 30 L of 95% ethanol and extracted at 50 ° C. for 24 hours. This was filtered through filter paper, dried and concentrated under reduced pressure at 45 ° C. to obtain 475 g of the total extract, and stored at −20 ° C.

Example 2 Effect of Root Extract on Growth of Brain Cancer Cells

In order to determine the effect of the conjugated extract extracted in Example 1 on the growth of brain cancer cells, Alamar Blue analysis was performed on U-87 MG, a human brain cancer cell. The Alamar Blue assay is a modified form of the MTT assay, in which a specific enzyme degrades a living cell and then measures the fluorescence intensity of the product as the compound breaks down to determine the relative number of living cells after treatment. I am an experimental method. It is described in more detail below.

<2-1> Preparation and Processing of Human Brain Cancer Cell Lines

U-87 MG cells, a brain cancer cell line used in the present invention, were distributed from the Korean Cell Line Bank (KCLB) and used for experiments. MEM (Minimal Essential Medium) containing 10% FBS (fetal bovine serum, fetal bovine serum) (Welgene) and 25 mM HEPES (4- (2-hydroxyethyl) -1-piperazineethanesulfonic acid) Cultured in the medium. The cells were maintained at 37 ° C. with 5% CO 2 water and passaged for 2-3 days.

<2-2> Cell growth inhibition measurement of U-87 MG cells

The vitrified extract extracted in Example 1 confirmed the cell growth inhibitory effect on U-87 MG, a brain cancer cell. Specifically, 8.0 x 10 per each well in a 96 well plate³ Said mucination in which U-87 MG cells were seeded and dissolved in dimethyl sulfoxide (DMSO) When the ethanol extract was treated at concentrations of 0 to 100 μg / ml (specifically, concentrations of 0, 3.125, 6.25, 12.5, 25, 50 and 100 μg / ml, respectively) for 48 hours, the degree of inhibition of cell growth was confirmed. (Table 1). After treatment of each concentration of extract, 20 μl of Alamar Blue reagent was added to 0.2 ml of cell culture filled in each well in a 96-well plate, and the plates were incubated for 2 hours in an incubator. The plate was slowly shaken to uniformly react the cells of each well, and the intensity of fluorescence was measured by Fluorescence Microplate Reader (Molecular Devices Corp.) at 590 nm while irradiating irradiated light at a wavelength of 544 nm. The viability of the cells is shown in FIG.

Table 1

Capacitive concentration	Brain cancer cell survival rate (average)	Standard Deviation
0 μg / ml	1.000	0.000
3.125 μg / ml	1.108	0.024
6.25 μg / ml	1.010	0.095
12.5 μg / ml	0.903	0.081
25 μg / ml	0.614	0.073
50 μg / ml	0.415	0.077
100 μg / ml	0.266	0.022

As a result, as shown in Table 1 and Figure 1, the higher the treatment concentration of the reduction of the brain cancer cell growth was reduced, it can be seen that the reduction has a brain cancer treatment effect. That is, brain cancer cells were killed at 9.7% at 12.5 μg / ml, 38.6% at 25 μg / ml, 58.5% at 50 μg / ml, and 73.4% at 100 μg / ml. In addition, the EC ₅₀ (half maximal effective concentration) was determined to be 25.132 μg / ml. Table 1 above describes the relative cell numbers of brain cancer cells after 48 hours according to the concentration of each of the retrograde treatments based on the number of survival rates of the brain cancer cells of the control group not treated with the retrograde. As such, the mussel extract of the present invention demonstrates superior U-87 MG cell killing activity and further has brain cancer treatment and prophylactic activity.

Example 3 Acute Toxicity Test with Root Extract

The mucination used in the present invention was widely used as a medicinal herb, so it was judged that there would be no problem in stability.

Acute toxicity test was performed using 6-week-old SPF SD rats. Two animals per group were suspended orally administered at a dose of 5 g / kg in suspension of the capillary extract of Example 1 of the present invention in 0.5% methylcellulose solution, respectively. After administration of the test substance, mortality, clinical symptoms, and changes in body weight were observed. Hematological and hematological examinations were performed. Necropsy was performed to observe abdominal and thoracic organ abnormalities.

As a result, there were no clinical symptoms or deaths in all animals treated with the test substance, and no toxicity change was observed in weight change, blood test, blood biochemistry test, autopsy findings, etc. As a result, all the extracts did not show toxic changes up to 5 g / kg in rats, and the minimum oral dose (LD ₅₀ ) was determined to be a safe substance of 5 g / kg or more.

Comparative Example 1

 Turmeric is a substance that shows anticancer activity against various kinds of cancers such as lung cancer, uterine cancer and breast cancer. The present inventors confirmed the effectiveness of the capillary extract of the present invention by confirming the extent to which the turmeric affects the growth of brain cancer cells.

Specifically, 3 kg of turmeric (domestic) purchased from Seoul Herbal Medicine was dried and ground for 5 days at the shade and room temperature. The ground turmeric was immersed in 30 L of 95% ethanol and extracted at 50 ° C. for 24 hours. This was filtered through a filter paper, dried and concentrated under reduced pressure at 45 ° C. to obtain 474 g of a total extract, which was stored at −20 ° C.

The turmeric extract was confirmed the growth inhibition of the U-87 MG cells in the same manner as in Example 2, and the results are shown in Table 2 and FIG.

TABLE 2

Turmeric concentration	Brain cancer cell survival rate (average)	Standard Deviation
0 μg / ml	1.000	0.000
3.125 μg / ml	1.020	0.076
6.25 μg / ml	1.042	0.097
12.5 μg / ml	1.060	0.092
25 μg / ml	1.021	0.081
50 μg / ml	0.987	0.090
100 μg / ml	0.913	0.029

As a result, as shown in Table 2, turmeric hardly reduced the growth of brain cancer cells even when the treatment concentration was high. As such, turmeric, which is widely known as an anticancer substance, has almost no brain cancer treatment efficacy, whereas the mucosa extract of the present invention has excellent U-87 MG cell killing activity, and further shows that it has brain cancer treatment and prophylactic activity.

<Preparation Example 1> Preparation of a brain cancer treatment agent containing the sundae extract as an active ingredient

The inventors of the present invention confirmed that the superior effect of the anticancer extract for the brain cancer treatment, and prepared a brain cancer treatment containing the extract as an active ingredient as follows. In addition, the preparation of the following therapeutic agent can be used for the application of the health food as well as the therapeutic agent.

<1-1> Soft Gelatin Capsules Containing Root Extract

20% extract, vitamin C 4.5%, vitamin D ₃ 0.001%, manganese sulfate 0.1%, beeswax 10%, palm oil 25%, safflower seed oil 30.399%

 <1-2> Preparation of Intravenous Formulations Containing Root Extract

Liquor extract 0.2%, mannitol 0.3%, saline 9.5%

<1-3> tablet containing the extract

Lilac Extract 35%, Vitamin C 10%, Vitamin D ₃ 0.001%, Manganese Sulfate 0.1%

Crystalline cellulose 25.0%, lactose 17.999%, magnesium stearate 2%

Preparation Example 2 Preparation of Functional Foods Containing Lilac Extract as Active Ingredient

The present inventors have confirmed that the sensitized extract is excellent in the brain cancer treatment activity through the above embodiment to prepare a functional food containing it as an active ingredient as follows.

<2-1> Preparation of Drink

The above composition of 522 mg of honey, 5 mg of thioctoamide, 10 mg of nicotinic acid, 10 mg of riboflavin hydrochloride, 2 mg of pyridoxine hydrochloride, 2 mg of inositol, 50 mg of orthoic acid, 0.48-1.28 mg of capillary extract, and 200 ml of water And the contents were prepared using conventional methods.

<2-2> production of chewing gum

Chewing gum was prepared using a conventional method using the composition and the content of 20% of gum base, 76.36 to 76.76% of sugar, 0.24 to 0.64% of pear extract, 1% of fruit flavor, and 2% of water.

<2-3> Preparation of Candy

Candy was prepared by the conventional method using the composition and content of 50-60% of sugar, 39.26-49.66% of starch syrup, 0.24-0.64% of bokbok extract, and 0.1% of orange flavor.

<2-4> Preparation of Biscuits

Force primary 88 kg, gravity primary 76.4 kg, white sugar 16.5 kg, salt 2.5 kg, glucose 2.7 kg, palm shortening 40.5 kg, ammo 5.3 kg, medium sodium 0.6 kg, sodium bisulfite 0.55 kg, rice flour 5.0 kg, vitamin B1 0.003 kg , 0.003 kg of vitamin B2, 0.16 kg of milk flavor, 71.1 kg of water, whole milk powder 4 kg, substitute milk powder 1 kg, calcium phosphate 0.1 kg, spray salt 1 kg, spray oil 25 kg, extract of 0.2 ~ 0.5 kg Biscuits were prepared using conventional methods in terms of composition and content.

<2-5> Preparation of Ice Cream

Milk fat 10.0%, nonfat milk solids 10.8%, sugar 12.0%, starch syrup 3.0%, emulsifying stabilizer (span, span) 0.5%, fragrance (strawberry) 0.15%, water 63.31 ~ 62.91%, capella extract 0.24 ~ 0.64% Ice cream was prepared using conventional methods using the above composition and content.

<2-6> manufacturing of chocolate

With the above composition and content of sugar 34.36 to 34.76%, cocoa butter 34%, cocoa mass 15%, cocoa powder 15%, lecithin 0.5%, vanilla flavor 0.5%, extracts 0.24 to 0.64%, using conventional methods Chocolate was prepared.

On the other hand, the specific scope of the present invention is defined by the claims rather than the embodiments described above, all changes and modifications derived from the meaning and scope and equivalent concepts of the claims to the scope of the invention It should be interpreted as including.

Claims (7)

1. Brain cancer prevention and treatment composition comprising the active ingredient extracted with the organic solvent.
2. The composition for preventing and treating brain cancer according to claim 1, wherein the organic solvent is ethanol.
3. The composition for preventing and treating brain cancer according to claim 2, wherein the active ingredient extracted with ethanol is extracted for 24 hours at 50 ° C.
4. According to claim 3, wherein the ethanol extract is brain cancer prevention and treatment composition, characterized in that the dried and concentrated under reduced pressure conditions 45 ℃.
5. The composition for preventing and treating brain cancer according to any one of claims 1 to 4, wherein the composition comprises a pharmaceutically acceptable carrier or diluent.
6. The composition of claim 1, wherein the composition is selected from a primary brain cancer population consisting of neuroma, astrocytoma, neuroblastoma, glioma, meningioma, oligodendrocyte, stromal blastoma, spinal cord tumor and neuromyoma. Brain cancer prevention and treatment composition, characterized in that applied to brain cancer.
7. Functional food for the prevention of brain cancer, comprising as an active ingredient extract of the organic solvent containing a food supplement acceptable food supplement.

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