WO2018052171A1 - Composition de traitement du cancer gastrique, contenant un extrait de larmes de job, et son procédé d'extraction - Google Patents

Composition de traitement du cancer gastrique, contenant un extrait de larmes de job, et son procédé d'extraction Download PDF

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Publication number
WO2018052171A1
WO2018052171A1 PCT/KR2017/001589 KR2017001589W WO2018052171A1 WO 2018052171 A1 WO2018052171 A1 WO 2018052171A1 KR 2017001589 W KR2017001589 W KR 2017001589W WO 2018052171 A1 WO2018052171 A1 WO 2018052171A1
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Prior art keywords
gastric cancer
root
composition
yulmu
dried
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PCT/KR2017/001589
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English (en)
Korean (ko)
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김태근
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김태근
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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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • A61K36/8994—Coix (Job's tears)
    • 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
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/308—Foods, ingredients or supplements having a functional effect on health having an effect on cancer prevention
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/20—Natural extracts
    • A23V2250/21—Plant extracts

Definitions

  • the present invention relates to a composition for treating gastric cancer comprising the extract of Yulmu and a method for extracting the same, and more particularly to a composition for treating gastric cancer comprising the water or alcohol extract of Yulmu seed effective for cancer cell death and anticancer. It is about.
  • Free radicals are naturally present in the body, and antioxidant enzymes that reduce excessive free radicals already exist in the body, such as enzymes such as SOD (Superoxide Dismutase), Catalase, Peroxidase, and Glutathione Peroxidase.
  • SOD Superoxide Dismutase
  • Catalase Catalase
  • Peroxidase Peroxidase
  • Glutathione Peroxidase a lot of free radicals occur in the body more than the allowable amount, the reaction rate of free radicals outpaces the rate of cell regeneration, and if the free radicals are not properly removed will have a significant effect on normal cells.
  • Free radicals denature the lipid membranes of cells to attack nucleic acids such as RNA and DNA in the cells to promote oxidation, induce protein peroxidation, thereby lowering the function of enzymes and hormones in the body and causing gene modification.
  • Antioxidants give electrons to these free radicals and stop the chain electron deprivation process.
  • antioxidant enzymes are inferior to the body or excessive free radicals are produced, eating antioxidant-rich foods causes cell oxidation. It is said that it is possible to prevent the progression of malignant cells, and for this reason, it is widely recommended to eat fruits and vegetables that are high in antioxidants.
  • Aged cells undergo apoptosis or programmed cell death, which kills themselves quickly and cleanly in certain situations.
  • the self-killing process is essential for preventing normal cells from changing abnormally and maintaining a constant number of cells.
  • the occurrence of various cancers is a case where apoptosis does not occur properly, and the destruction of the apoptosis mechanism due to genetic modification is a major cause of the change of normal cells into cancer cells (Hu and Kavanagh, 2003).
  • apoptosis in cancer cells by directly or indirectly increasing the activity of the Bcl2 family proteins, caspases and Tumor necrosis factor (TNF) -related apoptosis-inducing ligand (TRAIL) proteins (LeBlanc and Ashkenazi, 2003; Baetu and Hiscott, 2002; Trauzold et al., 2001).
  • TNF Tumor necrosis factor
  • TRAIL Tumor necrosis factor
  • apoptosis may be induced by targeting protein kinase, dephosphorylation enzymes, transcription factors, receptors on cell surface, and proteosomes (Jaattela, 2002; Reed, 2002).
  • Korean Patent No. 10-1047898 has proposed an anticancer composition comprising a zelkova tree methanol extract which induces cancer cell death using the zelkova extract as an active ingredient.
  • Republic of Korea Patent No. 10-1082599 has the effect of extracting constituent sugars, constituent amino acids, vitamins, minerals, etc. which are the active ingredients of the taste mushroom fruit body, electron donating ability (antioxidant), SOD-like activity, AGS human gastric cancer cell growth inhibition effect
  • Antioxidant and anti-cancer cancer compositions using mushrooms are proposed.
  • Yulmu (Coix lachrymajobi var. Mayuen) used as a main ingredient in the present invention is a perennial herb of rice family and its origin is known as Southeast Asia or China, and there is a record that it came from Song Dynasty in 1078 in Korea. Yulmu is about 1 ⁇ 1.5m long, flowers bloom in July, and fruits are harvested in autumn. Yulmu is known to be effective in the treatment of arthritis because it has the effect of smoothing the body's water metabolism and soothing swelling, and it helps metabolism smoothly, and it is also helpful in the discharge of waste products and has anti-inflammatory and analgesic effects. It is also effective in treating inflammation.
  • Yulmu's ingredients are high in potassium and rich in minerals. Therefore, Yulmu consumes sodium, which causes edema, and is effective in removing toxins and lowering blood pressure. Yulmu contains about 15g of protein per 100g, which is about twice as much as brown rice, and has a high content of essential amino acids such as lysine and tryptophan, which can be a good source of quality protein. It contains more than twice as many benefits, such as to help relieve cataracts and macular degeneration.
  • Elm (Ulmus davidiana Planch. Var. Japonica (Rehd.) Nakai) used in the present invention is a deciduous large tall tree growing near the valley of the whole country, the height of 15-25m, the stem bark is dark gray. Corks often develop on young branches, leaves are oval or obovate, 3-10cm long, 2-6cm wide, with cogs on the edges, green on the front, light green on the back. Flowers bloom before leaves in April-May, fruits ripen in May-June, 1.0-1.5 cm long, with wings.
  • Mallotus japonicus of the present invention grows mainly on the beach. It reaches a height of 10m. When young, it is covered with scaly hairs, turning reddish to grayish white, and its branches are thick. Leaves are alternate, egg-shaped, usually reddish on the surface, yellowish brown on the back, leaves edge is flat or slightly divided into three, and petioles are long.
  • the bark of the viburnum contains polyphenols and flavonoids such as Bergenin, Tannin and Rutin, which are excellent for antioxidant, anticancer, anti-inflammatory, suppressing gastric secretion, improving gastric ulcer, antiviral action, strengthening immunity and protecting liver.
  • the creation used in the present invention is made of the root stems of perennial herbaceous plants Atractylodes japonica KOIDZ. Et. KITAGAWA, A. lancea DC., A. chinensis KOIDZ. It is a medicinal herb that contains 5-9% of essential oils. The taste is bitter and very mild.
  • the gastrointestinal tract of our body is reluctant to its original moisture, but it has an excellent response to treat digestive disorders and gastrointestinal weakness caused by excessive accumulation of moisture in the stomach, pain in the stomach due to gastrointestinal disorders, decreased appetite and stomachache. There is a noticeable effect on the symptoms that complain. In particular, it is said to be a good treatment when the limbs are drowsy and heavy with vomiting, diarrhea and dysentery.
  • the present inventors searched for detoxifying enzyme activity in edible natural products to develop chemical cancer prevention substances that are non-toxic or weak in humans, while the leaves and stems of Yulmu, the roots and berries of Yulmu, the bark and the roots of elm, Yek It was confirmed that the composition extracted from the mixture of dried bark and root and the root of the production showed a specific and high apoptosis activity against gastric cancer cells, thereby confirming its potential as an anticancer agent against gastric cancer. In addition, the composition containing this as an active ingredient has completed the present invention by revealing that it can be used as a medicine and health functional food for the prevention or improvement of stomach cancer.
  • the present invention provides a pharmaceutical composition for the prevention and treatment of gastric cancer by using water or alcohol of Yulmu as a solvent, and furthermore, based on 46 to 66% by weight of dried Yulmu fruit powder. 14 to 24% by weight of dried elm bark and roots in a 1: 1 weight ratio, 14 to 24% by weight of dried bark and roots in a 1: 1 weight ratio and dried Produced by the roots of the compound consisting of 2.5 ⁇ 7% by weight of the pulverized extract and the fermentation of the formulation by alcohol and fermentation using alcohol for the provision of a pharmaceutical composition for the prevention and treatment of gastric cancer extracted and a method for producing the same.
  • Gastric cancer treatment composition comprising the extract according to the present invention prepared as described above can be used for the purpose of health supplements for the treatment of gastric cancer and gastric cancer with little side effects.
  • Figure 3 is a toxicity evaluation of the cell line of Yulmu blend water extract
  • composition for treating gastric cancer comprising the extract of Yulmu of the present invention and an extraction method thereof will be described in detail.
  • the inventors of the present invention directly confirmed that the condition improved after taking Yulmu while searching for an anticancer drug of stomach cancer that is safe for the human body to overcome stomach cancer based on the experience that he suffered from stomach cancer without surgery.
  • he conducted anticancer experiments on the stems and roots of yulmu, and further formulated the mixture including the bark and roots of the elm tree, the bark and the roots of elm trees, which are beneficial to gastrointestinal diseases. The effect analysis was performed.
  • Yulmu fruit was generally harvested in autumn and dried in the sun to make a blend containing jujuk radish.
  • the bark and roots of elm and elder tree were shaded to prevent changes in the composition under the influence of UV rays during the drying process. After drying at, the weight ratio of skin and roots was mixed to be 1: 1, and creation was used by purchasing dried creation that is commercially available.
  • Nuruk is mixed into the formulation prepared as described above in a weight ratio of 3: 1 to 7: 1, preferably 5: 1, and 70 to 90% by weight of water of the mixture containing the Nuruk is mixed and placed in a dock. It fermented for 3 to 15 days at the temperature of 38 degreeC. If the fermentation temperature is low, a long fermentation period is required, and the higher the temperature, the shorter the fermentation period, and preferably, the fermentation is performed at a temperature of 35 ° C. to 36 ° C. for about 5 days to 7 days. The fermented formulations were dried in the shade to make fermented formulations.
  • Extraction of yulmu and yulmu blend is preferably an extract obtained by extracting dried plants of each plant with water, alcohols of C 1 to C 4 or a mixed solvent thereof, and most preferably with ethanol which is less toxic to the human body during oxidation. It may be an extracted extract.
  • Each sample, the compound and the fermented compound of Yulmumu were ground to an appropriate size, placed in an extraction container, and then poured into a lower alcohol of C 1 to C 4 or a mixed solvent thereof, preferably ethanol, and the solution was boiled under reflux and left for a predetermined time. Then, filtered through a filter paper and the like to obtain an alcohol extract.
  • the extraction time is preferably 2 to 12 hours, most preferably 3 to 5 hours. Thereafter, a method such as concentration or lyophilization may be further roughened.
  • composition for treating gastric cancer of the present invention may include each of the above active ingredients alone, and may further include a pharmacologically acceptable carrier or excipient according to the formulation, method of use, and purpose of use.
  • the carrier or excipient includes water, dextrin, calcium carbonate, lactose, propylene glycol, liquid paraffin, physiological saline, dextrose, sucrose, sorbitol, mannitol, ziitol, erythritol, maltitol, starch, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, polyvinylpyrrolidone, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oils, which may be used one or more, but are not limited thereto, and common carriers and Excipients can all be used.
  • the pharmaceutical composition may further include conventional fillers, extenders, binders, disintegrants, surfactants, anti-coagulants, lubricants, wetting agents, fragrances, emulsifiers or preservatives.
  • composition for treating gastric cancer is formulated into a tablet, capsule, chewing tablet, granule, powder, liquid solution, suspension, dispersion, emulsion, syrup, etc., gum arabic, corn starch, Binders such as microcrystalline cellulose or gelatin, excipients such as dicalcium phosphate or lactose, disintegrants such as alginic acid, corn starch or potato starch, lubricants such as magnesium stearate, sweeteners such as sucrose or saccharin and peppermint, methyl Flavoring agents, such as salicylates or fruit flavors, may be included.
  • a liquid carrier such as polyethylene glycol or fatty oil may be included.
  • the pharmaceutical composition for the prevention and treatment of gastric cancer containing the extract of the formulation containing the yulmu fruit according to one embodiment of the present invention as an active ingredient may be used as a health functional food to protect the stomach.
  • Health functional foods that protect the stomach include, for example, granules, syrups, caramel products, candy, confectionery, various foods such as chewing gum, beverage products such as soft drinks, mineral water, alcoholic beverages, vitamins and minerals, and the like. Health functional food.
  • the dosage of the composition for treating gastric cancer according to the present invention may be determined in consideration of the administration method, the age, sex and weight of the recipient, and the severity of the disease.
  • Examples of toxicity evaluation against gastric cancer cells using the AGS gastric cancer cell line of the yulmu extract and yulmu combination of the present invention are described. Experiments were first conducted to analyze the stomach cancer cells by making a composition extracted from water and ethanol with extracts of Yulmu outpost, root and fruit, and then dried dried bark and roots. Toxicity experiments were carried out on gastric cancer cells using a composition obtained by fermenting the dried bark and roots and creating a blend of fermented blends prepared by fermenting the blend with Nuruk.
  • Sample preparation Dissolve 50 mg of each extract of Yulmu starch, fruit and root extract in water in 1 ml of DMSO, a dissolution aid (1 min), store it at -20 ° C, and 50mg of Yulmu starch, fruit and root extract extracted with 95% ethanol. It was dissolved in 1 ml (1 min) and stored at -20 ° C.
  • Culture medium RPMI-1640 medium 500 ml, 10% Fetal Bovine Serum, 1% P / S
  • AGS cells which are gastric cancer cells, were inoculated in 96 well plates at 50,000 cells / well for each well and incubated for 24 hours.
  • each sample was treated in each well by concentration, and then cultured for 24 hours. At this time, a medium except Fetal Bovine Serum was used.
  • the toxicity was determined based on this.
  • 600 g of dried Yulmu fruit is the main ingredient, 200g of elm bark and roots are dried in the shade by adding 1: 1 weight ratio, and 200g dried in the shade and 50g of dried produce in the shade. 1050 g of the compound before fermentation was prepared by mixing and crushing each using a grinder.
  • 500 g was removed from the compound before fermentation, placed in a bowl, 100 g of Nuruk was mixed, 480 g of water was mixed, fermented at a temperature of 35 ° C. for 7 days, and the fermented mixture was dried in the shade to prepare a compound after fermentation.
  • Extracts were prepared by repeating three times using reflux cooling with water and 95% ethanol as a solvent using the pre-fermentation and post-fermentation formulations.
  • Sample preparation 50 mg of each extract of the pre-fermentation compound and the post-fermentation compound were dissolved in 1 ml of DMSO (1 min), stored at -20 ° C, and extracted before the fermentation of the compound and extracted after fermentation with 95% ethanol. 50 mg of each extract of the combination was dissolved in 1 ml of DMSO (1 min) and stored at -20 ° C.
  • Culture medium RPMI-1640 medium 500 ml, 10% Fetal Bovine Serum, 1% P / S
  • gastric cancer cells AGS cells were inoculated in 96 well plates at 50,000 cells / well for each well and incubated for 24 hours.
  • each sample was treated in each well by concentration, and then cultured for 24 hours. At this time, a medium except Fetal Bovine Serum was used.
  • the toxicity was determined based on this.
  • the pre-fermentation extract of fermented non-fermentation shows a survival rate of 80% or more up to 50 ⁇ g / ml concentration, but the concentration will be increased
  • the lower the survival rate the more gastric cancer cells became close to annihilation at 200 ⁇ g / ml concentration, and after fermentation, gastric cancer cells showed more than 80% survival under 12.5 ⁇ g / ml concentration. It was.

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Abstract

La présente invention concerne une composition de prévention et de traitement du cancer gastrique, contenant de la racine et du fruit de larmes de job, et son procédé de préparation. La présente invention concerne l'extraction d'une composition destinée à prévenir et à traiter le cancer gastrique à partir de racine et de fruit de larmes de job en utilisant de l'eau ou un alcool comme solvant et, en outre : la préparation d'une composition de prévention et de traitement du cancer gastrique, obtenue par extraction, en utilisant un alcool, d'un mélange contenant de 46 à 66 % en pds d'un produit pulvérisé de fruit de larmes de job séché comme ingrédient principal, de 14 à 24 % en pds d'un produit pulvérisé dans lequel les écorces et les racines d'orme sec sont mélangées sous un rapport en poids de 1:1, de 14 à 24 % en pds d'un produit pulvérisé dans lequel les écorces et les racines de Mallotus japonicus séché sont mélangées sous un rapport en poids de 1:1, et de 2,5 à 7 % en pds d'un produit pulvérisé des racines séchées de rhizome d'Atractylodes, et par fermentation du mélange avec de l'éthanol brut et ensuite sa fermentation en utilisant de l'alcool ; et son procédé de préparation.
PCT/KR2017/001589 2016-09-19 2017-02-14 Composition de traitement du cancer gastrique, contenant un extrait de larmes de job, et son procédé d'extraction WO2018052171A1 (fr)

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KR10-2016-0119470 2016-09-19
KR1020160119470A KR101706552B1 (ko) 2016-09-19 2016-09-19 율무 추출물을 포함하는 위암 치료용 조성물과 그 추출방법

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CN108721446A (zh) * 2017-04-22 2018-11-02 邓泽潭 一种治疗胃癌的内服中药
KR101931609B1 (ko) * 2017-06-05 2018-12-21 대한민국 율무 새싹 추출물을 유효성분으로 하는 암 예방 또는 치료용 조성물

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