KR20130025602A - Composition for anticancer drugs comprising an extract of morus bombycis koidz - Google Patents
Composition for anticancer drugs comprising an extract of morus bombycis koidz Download PDFInfo
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- KR20130025602A KR20130025602A KR1020110089007A KR20110089007A KR20130025602A KR 20130025602 A KR20130025602 A KR 20130025602A KR 1020110089007 A KR1020110089007 A KR 1020110089007A KR 20110089007 A KR20110089007 A KR 20110089007A KR 20130025602 A KR20130025602 A KR 20130025602A
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- South Korea
- Prior art keywords
- extract
- mulberry
- oxyresveratrol
- active ingredient
- cancer
- Prior art date
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/60—Moraceae (Mulberry family), e.g. breadfruit or fig
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/308—Foods, ingredients or supplements having a functional effect on health having an effect on cancer prevention
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/58—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation
- A61K2039/585—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation wherein the target is cancer
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Botany (AREA)
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- Chemical & Material Sciences (AREA)
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Abstract
The present invention is mulberry ( Morus bombycis koidz ) oxyresveratrol , an active ingredient of the extract of the mulberry family, is characterized by including the development of an anticancer agent and a health functional food composition comprising the same as a component having a pharmacological action of cell proliferation inhibition.
Description
The present invention is Morus ( Morus) bombycis koidz ) The present invention relates to an anticancer composition containing an active ingredient of the mulberry family extract oxyresveratrol and a health functional food composition comprising the same.
Among many diseases that humanity has not overcome, cancer is known as the most threatening disease for us. This is a common research task in almost all countries, not only Korea, but also the United States and Japan. Even after more than 30 years of in-depth research on cancer, the incidence of cancer continues to increase due to environmental pollution and poor dietary habits. In 2020, about 15 million people worldwide occur every year. The World Health Organization (WHO) One of the main causes is cancer.
In addition, as the disease of the middle-aged people more than 60% is diagnosed at 60 years of age or older, the incidence of cancer increases as the world population ages. The US Centers for Disease Control and Prevention recently reported a rapid increase in the number of cancer patients in the United States, resulting in one cancer patient per 20 Americans, and according to statistics from the Ministry of Health and Welfare, more than 130,000 cancer patients are increasing every year. Reported. When Koreans survive to life expectancy at 80 years of age, the probability of cancer is 34%, indicating that 1 in 3 people will have cancer, while in the United States, 1 in 2 men and 1 in 3 women have cancer. statistics, 2010, CA Cancer J Clin 2010].
The human body is composed of about 60 trillion cells, and more than 100 types of cancers occur in the human body. Cancers are classified into three groups, such as epithelial tumors, sarcomas, and leukemias or lymphomas. About 90% of human cancers are epithelial tumors and are derived from epithelial cells of ectoderm or endoderm. Cancer is known to be one of the refractory diseases because the origin of the cancer is known and can be classified, but its mechanism is still unclear.
Cancer has multiple stages, such as initiation, promotion, progression, and metastasis. Chemical cancer prevention is primarily aimed at suppressing cancer initiation and promotion. According to the mechanism was divided into two. That is, a blocking agent having a mechanism for inhibiting the carcinogen reacting with the intracellular target or reaching the target and a suppressing agent for suppressing the process in which the cells exposed to the carcinogen appear as neoplasia. It can be divided into (suppressing agent). Blocking agents include diallyl sulfide, isothiocyanate, and ellagic acid, inhibitors of the cytochrome P-450 enzyme. Phenylethyl isothiocyanate, sulforaphane, oltipraz, etc. which are detoxification enzyme-based inducers are known. Suppressing agents include DFMO as a polyamine metabolism inhibitor, retinoid family as a cell differentiation promoter, genistein as a protein kinase C inhibitor, and EGCG as an inhibitor of oxidative DNA damage. have.
There are three general treatments for cancer: surgical surgery, radiation therapy, and drug therapy. Surgical surgery can be applied at various stages of cancer. Early stage cancers can be treated with surgical procedures, but if the cancer has advanced or metastasized, surgical treatment alone will be difficult to treat. Radiation therapy treats cancer by irradiating the cancer cells with X-rays or γ-rays from external radiation or radioactive substances administered into the body. Radiation therapy is used to treat areas that are difficult to operate or for radiation-sensitive cancer. Drug treatment is a method of destroying or inhibiting DNA or related enzymes necessary for the proliferation of cancer cells by administering oral or injection anticancer drugs. Although these treatments induce cancer cell death by DNA damage, cell stress, DNA replication inhibition, and cell division, these treatments have side effects after repeated treatments, they are resistant to cancer, and are difficult to cure. In reality, when the diagnosis of cancer is delayed or the cancer has spread, the treatment method is complicated and the mental and economic burden of the treatment may be much greater.
Anticancer drugs currently used in cancer treatment act on cancer cells with rapid division and proliferation rate, so they are easily toxic to bone marrow cells, gastrointestinal mucosa, and hair cells, which grow rapidly among normal cells. In particular, bone marrow cells play an important role in producing various blood cells, and thus suppressing bone marrow function has major side effects that limit the dose of cytotoxic anticancer drugs. It was urgent.
The present inventors have completed the present invention by confirming the anti-cancer effect of the active ingredient oxyresveratrol of the mulberry stem extract, by testing a variety of indicators of various anticancer effects.
Thus, one example of the present invention is a mulberry ( Morus bombycis koidz ) provides an anticancer composition containing the active ingredient oxyresveratrol of plant extracts.
Another example relates to a health functional food composition comprising the active ingredient oxyresveratrol of the wild mulberry extract.
Another example relates to a method for preparing an anticancer agent composition comprising the active ingredient oxyresveratrol of the extract of the mulberry tree.
The inventors of the present invention used oxyresveratrol as an active ingredient of the extract of the stem of the mulberry tree. morphological changes were observed under the light microscope after 24 hours of oxyresveratrol as an active ingredient of the extract in the cell), and CCK-8 assay was performed to investigate the anticancer effect. .
Wild mulberry ( Morus bombycis koidz ) An anticancer composition containing the active ingredient oxyresveratrol of the stem mulberry family extract is provided.
In another example,
Preparing a dried mulberry plant; And
Provided is a method for producing the anticancer composition comprising the step of extracting in aqueous solution by adding one or more solvents selected from the group consisting of water and alcohols having 1 to 4 carbon atoms to the dried mulberry family.
This will be described in more detail below.
Mountain Mulberry (Morus bombycis koidz ) also grows on mulberry and deciduous trees or shrubs. The leaves are regenerated, ovate or frenzied, somewhat thick and glossy, The lower part of leaves is divided into 3 ~ 5 branches, 6 ~ 14cm long and 3 ~ 9cm wide. The leaf edge has serrations, the surface is green and hairless, the back side is light green, and hair is on the vein. Flowers bloom in April-June and are bivalve or mixed flowers, and male flowers are gathered in long watery inflorescences, with 4 stamens and 4 flower-covered pieces. Female flowers have pistils with 2 pistils, but the pistils are almost none. Fruits are elliptical or oblong in June, 5 ~ 14mm long, ripen in red or black purple. Trees reach 12m high and usually grow in forests below 1000m above sea level. It is native to China and grows or grows in Korea. A plant belonging to the Moraceae seomppong (Var. Maritima koidz ), tail mulberry ( Var . caudatifolia koidz ), wild mulberry ( Morus bombycis koidz ) and the like, in the embodiment of the present invention was used for the mulberry ( Morus bombycis koidz ).
Mulberry family extract of the present invention is obtained by extracting the entire plant, or a part of the plant (roots, leaves, flowers, stems, berries, etc.), such as the ground part of the plant (leaves, flower stems, berries), preferably extract the stem It may be obtained by. To date, there is no known anticancer effect on the extract of the stem of the mulberry tree. In particular, the mulberry plant extract according to the present invention has the advantage that even when used alone without being used in combination with other active ingredients, sufficient anticancer effect.
Available in the present invention seomppong Moraceae plants (Var. Maritima koidz ), tail mulberry ( Var . caudatifolia koidz ) and the like may be one or more selected from the group consisting of.
The mulberry family plant extract may be obtained by extracting the stem of the plant with one or more solvents selected from the group consisting of water, alcohol having 1 to 4 carbon atoms.
In one embodiment, the extract of the mulberry stem is obtained by extracting the mulberry stem with an alcohol having 1 to 4 carbon atoms, preferably 60 to 95% (v / v) of 50 to 99.9% (v / v). It may be.
In the embodiment of the present invention, the extract obtained by extracting the stem of the mountain mulberry with 70 to 90% ethanol, but is not limited thereto.
In order that the active ingredient in the stem of the mulberry tree can be sufficiently extracted, the amount of the extraction solvent may be about 5 to 20 times, preferably about 7 to 15 times, based on the weight of the mulberry stem, and the extraction temperature is 50 to 100 ° C., Preferably it is in the range of 60 to 80 ℃, extraction time may be 1 to 10 hours, preferably 1 to 5 hours, but is not limited thereto.
The composition of the present invention is a nutrient, vitamin, electrolyte, flavoring agent, coloring agent, neutralizing agent, pectic acid and salts thereof, alginic acid and salts thereof, organic acid, protective colloid thickener, pH regulator, stable, It may further contain an agent, a preservative, glycerin, alcohol, a carbonation agent used in the carbonated beverage, and the like. The components can be added independently or in combination. The content of the additional component is preferably added in the range of 0.01 to 100 parts by weight per 100 parts by weight of the mulberry extract, but is not limited thereto.
The content of the mulberry extract in the composition can be appropriately adjusted according to the symptoms, the degree of symptoms, the condition of the patient, and the like, for example, 0.0001 to 99.9% by weight, preferably 0.001 to 50% by weight based on the total weight of the composition. Preferably, but is not limited thereto. The content ratio is a value based on the drying amount from which the solvent is removed.
The composition may further contain an appropriate carrier, excipient and diluent conventionally used in the production of a pharmaceutical composition. The composition may be administered orally or parenterally in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, Formulations, formulations, external preparations, suppositories or sterile injectable solutions, and the like.
When the composition is formulated, it is prepared using a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, or an excipient usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations may include at least one excipient and / or lubricant. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, suppositories, and the like.
The preferred dosage of the composition depends on the condition and weight of the patient, the severity of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. For a more preferable effect, the dosage of the composition of the present invention is preferably 1 mg / kg to 100 mg / kg per day based on the active ingredient, but is not limited thereto. The administration may be carried out once a day or divided into several doses. The compositions of the present invention may be administered to a mammal, including a human, in various ways. All modes of administration may be expected, for example, by oral, intravenous, intramuscular, subcutaneous injection, and the like. The pharmaceutical dosage form of the composition of the present invention may be used in the form of a pharmaceutically acceptable salt of the active ingredient, and may be used alone or in combination with other pharmaceutically active compounds as well as in a suitable combination.
In another example, there is provided a health functional food composition comprising the wild mulberry plant extract.
In the present invention, the term " food " means a natural product or a processed product containing one or more nutrients, preferably a state of being able to be directly eaten through a certain processing step, , Health functional foods, beverages, food additives and beverage additives. Examples of the foods include various foods, beverages, gums, teas, vitamin complexes, and functional foods. In addition, in the present invention, the food may contain special nutritional foods (e.g., crude oil, spirits, infant food, etc.), meat products, fish products, tofu, jelly, noodles (Such as soy sauce, soybean paste, hot pepper paste, mixed sauce), sauces, confectionery (eg snacks), dairy products (eg fermented milk, cheese), other processed foods, kimchi, pickled foods But are not limited to, fruits, vegetables, beverages, beverages, fermented beverages, ice creams, etc.), natural seasonings (eg, ramen soup, etc.), vitamin complexes, alcoholic beverages, alcoholic beverages and other health supplement foods. The health functional food, beverages, food additives or beverage additives may be prepared by a conventional manufacturing method.
The food composition may comprise a pharmaceutically acceptable food-aid additive and may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of a functional food.
In addition, in the food, the amount of the mulberry extract may be included as 0.00001% to 50% by weight of the total food weight, if the food is a beverage based on 0.001 g to 50 g based on the total volume of
The present invention relates to an anticancer agent composition, which is characterized by obtaining an anticancer effect using an active ingredient oxyresveratrol of the extract of the stem of the mulberry tree, which is meaningful in terms of the anticancer agent composition derived from natural products and when actively used, It can be widely used as an anticancer agent composition and can further contribute to national health.
Figure 1 shows that the active ingredient oxyresveratrol of the extract of the mulberry stem extracts cell growth inhibition and toxicity for each cell line (Mouse TR neocortical neuroblast cell, Rat embryo Rat-2 fibroblast cell, Rat B103 neuroblastoma cell, Human SH-SY5Y neuroblastoma cell) CCK-8 assay was performed to investigate. The active ingredient oxyresveratrol of the mulberry stem extract was treated in different cell lines at concentrations of 1.0, 10, 20, 30, 40, and 50 ug / ml, and cultured for 24 hours at 37 ° C, compared with the control without the mulberry stem extract. As a result of confirming the activity, the concentration of the active ingredient oxyresveratrol of the extract of the stem of the mulberry tree can be confirmed the potent cytotoxicity. This shows that the active ingredient oxyresveratrol of the extract of the stem of the mulberry tree has a high anticancer activity.
Figure 2 was analyzed by morphology of cancer cells after treatment at 37 ℃ for 24 hours in order to analyze the effect of the active ingredient oxyresveratrol of Ratberry stem extract to Rat neuroblastoma cell line (Rat B103 Neuroblastoma cell ) . As shown in the photograph, it can be observed that the morphological change appeared in a concentration-dependent manner compared to the control group not treated with the mulberry stem extract. In other words, it can be observed that not only the total number of cells, but also the condensation of the shape and the appearance of cell death with irregular shape.
Figure 3 is an active ingredient oxyresveratrol of the extract of the Mulberry stem extract to the effect of human neuroblastoma cell line (SH-SY5Y Neuroblastoma cell) treated by concentration incubated for 24 hours at 37 ℃ irradiated with light microscopy It was. As shown in the photograph, it can be observed that the apoptosis phenomenon appeared in a concentration-dependent manner compared to the control group not treated with the mulberry stem extract.
Figure 4 shows the active ingredient oxyresveratrol of the mulberry stem extract BrdU assay was performed to measure the change of S phase fraction of human neuroblastoma cell line (SH-SY5Y Neuroblastoma cell). After 24 hours of treatment at concentrations of 1, 30 and 40 ug / ml, the changes in the S phase fraction of cancer cells were statistically significant compared to the control group, and decreased with increasing concentration of the extract.
Hereinafter, the present invention will be described in more detail with reference to Examples. However, these examples are merely illustrative of the present invention, and the scope of the present invention is not limited by these examples.
Preparation of Mulberry Stem Extract
After drying the mulberry stem part, 10 times (v / v) of 70% (v / v) ethanol was added to 100 g of the dried mulberry stem by the weight, extracted at 70 ° C. for 3 hours, and then filtered. The mulberry stem extract was obtained. The extraction was repeated twice, and the extract was concentrated under reduced pressure at 40 ° C. or lower and then freeze-dried to obtain a powdery extract.
Active ingredient of wild berry stem extract oxyresveratrol Cytotoxicity experiments in each of these cell lines
Cell growth inhibition of cancer cells such as Mouse TR neocortical neuroblast cell, Rat embryo Rat-2 fibroblast cell, Rat B103 neuroblastoma cell, Human SH-SY5Y neuroblastoma cell And CCK-8 assay was performed to investigate the toxicity. Cytotoxicity was measured after 24-hour treatment of the active ingredient oxyresveratrol of the mulberry stem extract at a concentration of 1.0, 10, 20, 30, 40, 50 ug / ml. The control group was subjected to experiments under the same conditions using cancer cells treated with the same amount of DMSO instead of wild berry stem extract.
The obtained result is shown in FIG. Figure 1 shows a group of different cancer cells treated at concentrations of 1.0, 10, 20, 30, 40, 50 ug / ml compared to the control. As shown in FIG. 1, the wild mulberry stem extract was shown to have a significant decrease in cell viability due to the concentration-dependent decrease in cell growth inhibition and toxicity compared with the control group.
Active ingredient of wild berry stem extract oxyresveratrol this Rat Neuroblastoma cell line ( Rat B103 Neuroblastoma cell ) Cytotoxicity Experiment
The oxyresveratrol of the active ingredient oxyresveratrol prepared in Example 1 in rat rat neuroblastoma cell lines (Rat B103 Neuroblastoma cells) at a concentration of 1, 20 and 30 ug / ml, respectively, after 24 hours to optically change the morphological changes of cancer cells. It was examined under a microscope. As a control group, rat B103 Neuroblastoma cells treated with the same amount of DMSO instead of wild berry stem extract were conducted under the same conditions.
The obtained result is shown in FIG. Figure 2 is a photograph showing the morphological changes according to the treatment concentration of the active ingredient oxyresveratrol of the mulberry stem extract compared to the control. As shown in Figure 2, wild mulberry stem extract can be seen that the appearance of apoptosis significantly compared to the control.
Active ingredient of wild berry stem extract oxyresveratrol This human neuroblastoma cell line ( Human SH - SY5Y Neuroblastoma cell ) Cytotoxicity Experiment
To the active ingredient oxyresveratrol of the mulberry stem extract prepared in Example 1 Morphological changes of cancer cells 24 hours after treatment in human neuroblastoma cell lines (SH-SY5Y Neuroblastoma cells) at concentrations of 1, 30 and 40 ug / ml, respectively, were examined by light microscopy. As a control group, human SH-SY5Y Neuroblastoma cells treated with the same amount of DMSO instead of the extract of the stem of the mulberry tree were conducted under the same conditions.
The obtained results are shown in Fig. Figure 3 is a photograph showing the morphological changes according to the treatment concentration of the active ingredient oxyresveratrol of the mulberry stem extract compared to the control. As shown in Figure 3, the active ingredient oxyresveratrol of the mulberry stem extract can confirm the strong cytotoxicity compared to the control.
Active ingredient of wild berry stem extract oxyresveratrol This human neuroblastoma cell line ( Human SH - SY5Y Neuroblastoma cell ) In BrdU analysis
To the active ingredient oxyresveratrol of the mulberry stem extract prepared in Example 1 In order to measure the change in the S phase fraction of cancer cells 24 hours after treatment with human neuroblastoma cell lines (SH-SY5Y Neuroblastoma cells) at concentrations of 1, 30 and 40 ug / ml, the proliferation inhibitory effect of cancer cells was examined by BrdU staining. Analyzed. As a control group, human SH-SY5Y Neuroblastoma cells treated with the same amount of DMSO instead of the extract of the stem of the mulberry tree were conducted under the same conditions.
The obtained result is shown in FIG. Figure 4 is a photograph showing the cancer cell proliferation inhibitory effect according to the treatment concentration of the active ingredient oxyresveratrol of the mulberry stem extract compared to the control. As shown in Figure 4, wild mulberry stem extract can confirm the strong cancer cell proliferation inhibitory effect compared to the control.
Claims (5)
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103194493A (en) * | 2013-04-25 | 2013-07-10 | 湖南中医药大学 | Method for preparing Oxyresveratrol by utilizing microbial transformation |
| CN115212199A (en) * | 2022-05-24 | 2022-10-21 | 核工业总医院 | Application of small molecular compound in preparation of medicine for treating diffuse large B cell lymphoma |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103194493A (en) * | 2013-04-25 | 2013-07-10 | 湖南中医药大学 | Method for preparing Oxyresveratrol by utilizing microbial transformation |
| CN115212199A (en) * | 2022-05-24 | 2022-10-21 | 核工业总医院 | Application of small molecular compound in preparation of medicine for treating diffuse large B cell lymphoma |
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