WO2012050398A2 - Composition pharmaceutique comprenant un extrait de plantes médicinales pour la prévention ou le traitement du cancer du poumon - Google Patents

Composition pharmaceutique comprenant un extrait de plantes médicinales pour la prévention ou le traitement du cancer du poumon Download PDF

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WO2012050398A2
WO2012050398A2 PCT/KR2011/007676 KR2011007676W WO2012050398A2 WO 2012050398 A2 WO2012050398 A2 WO 2012050398A2 KR 2011007676 W KR2011007676 W KR 2011007676W WO 2012050398 A2 WO2012050398 A2 WO 2012050398A2
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lung cancer
composition
weight
parts
extract
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WO2012050398A3 (fr
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황성연
안성훈
서근영
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주식회사 한국전통의학연구소
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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)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • 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)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • 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)
    • A61K36/43—Cuscutaceae (Dodder family), e.g. Cuscuta epithymum or greater dodder
    • 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)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to a pharmaceutical composition for preventing or treating lung cancer, including a herbal extract, and more particularly, including an extract of red ginseng, Angelica, Schisandra chinensis, Tosa and turmeric as an active ingredient, having a high antioxidant activity, in particular,
  • the present invention relates to a pharmaceutical composition for preventing or treating lung cancer having an excellent anticancer effect on lung cancer.
  • Lung cancer (lung cancer) is the third most common cancer among the most common cancers in Korea, and the mortality rate from lung cancer is increasing rapidly while the mortality rate from gastric cancer and liver cancer has recently decreased.
  • the five-year survival rate of lung cancer is only 13%, which is known to have a poorer prognosis than any other cancer except for cancers of the pancreas, liver, and esophagus.
  • lung cancer An important risk factor for lung cancer is occupational exposure to smoking and other carcinogens. In particular, more than 90% of cancers in trachea and bronchus have been reported to result from smoking. have. Lung cancer is classified into non-small cell carcinoma and small cell carcinoma according to the microscopic cell types of cancer cells. Non-small cell lung cancer accounts for about 80% of all lung cancers. There are three subtypes of squamous cell carcinoma, adenocarcinoma and large-cell carcinoma.
  • Small cell lung cancer accounts for about 20% of all lung cancers, and it occurs first in the airways (bronchi or bronchioles). Carcinomas usually form along the surface or gland of the trachea, mostly in the center of the lung (4/5), and the remainder (1/5) in the periphery. The overall malignancy is so strong that it grows quickly and tends to metastasize away early through the lymphatic system or blood circulation. Surgery, radiation therapy and chemotherapy are used for the treatment of lung cancer, but in the case of non-small cell lung cancer, many patients recurred after surgery even in cases where complete surgical resection was possible. Long-term survival is possible only in%, 30-50% in stage 2, and 10-30% in stage 3. Overall, the 5-year survival rate is only 30% and the 10-year survival rate is only 15%. Many efforts are being made to improve the poor treatment results. Although some of the effects have been proven before and after surgery, the combination of chemotherapy or radiation therapy has caused some side effects, and the treatment rate is still unsatisfactory. .
  • DEN diethylnitrosamine
  • the "military clergy theory" ( ⁇ ⁇ ⁇ ) is the basic principle of the composition of the control, which is modeled after the rule of the ancient monarchy system. In oriental medicine, this principle is applied, and each ingredient plays a unique role to treat the whole harmony and balance.
  • Herbal medicines which were used for the treatment of various diseases, have not been developed as a method of refining them due to impurity, but they have been developed from simply taking one type of drug like Dokticianang to taking various types of drugs, suggesting a great development of liver control. can do.
  • Predecessors have recognized that there are a great variety of factors that control the human body, and it is more beneficial to control various factors in the body with different drugs than simply or one important factor in how to control disease or pain. It can be concluded that the empirical knowledge of the predecessors is concentrated.
  • the present inventors cultured A549 human lung cancer cell line to observe the effectiveness of the combination of red ginseng, Angelica, Schisandra chinensis, Tosa, and turmeric during the experiment of about 400 kinds of medicinal herbs. ⁇ ) to compare the effects on each cell proliferation and to examine the meaning based on the history of military affairs, in addition to the composition of wolfberry, cornus, bokbunja, red ginseng, wolfberry, cornus, Omija, bokbunja, earthenware, The present invention was completed by finding that the herbal extract of turmeric and donkey had the protective effect on lung tissue against stimulation of lung cancer caused by continuous oral administration of DEN.
  • a pharmaceutical composition for preventing or treating lung cancer comprising extracts of red ginseng, Angelica, Schisandra chinensis, Tosa and turmeric as active ingredients.
  • Another object of the present invention to provide a health functional food composition for preventing or improving lung cancer comprising the extract as an active ingredient.
  • the present invention provides a pharmaceutical composition for preventing or treating lung cancer comprising red ginseng, Angelica, Schisandra chinensis, Tosa and turmeric extract as active ingredients.
  • compositions for preventing or treating lung cancer characterized in that it further comprises a gojija, cornus and bokbunja extract in addition to the composition.
  • lung cancer prevention or improvement health functional food composition comprising the extract as an active ingredient.
  • the present invention provides a pharmaceutical composition for preventing or treating lung cancer, comprising extracts of red ginseng, Angelica, Schisandra chinensis, Tosa and turmeric as active ingredients.
  • the composition is based on 100 parts by weight of red ginseng, 100 to 500 parts by weight, Schisandra chinensis 50 to 200 parts by weight, earth and sand 20 to 200 parts by weight, turmeric in the pharmaceutical composition for preventing or treating lung cancer, characterized in that it comprises 20 to 200 parts by weight It is preferably a composition.
  • the present invention provides a pharmaceutical composition for preventing or treating lung cancer, characterized in that it comprises red ginseng, Angelica, Schisandra chinensis, Tosa, turmeric Wolfberry, Cornus and Bokbunja extracts.
  • the composition is 100 to 500 parts by weight of red ginseng, 50 to 200 parts by weight of Schisandra chinensis, 20 to 200 parts by weight of earthenware, 20 to 200 parts by weight of turmeric, 100 to 500 parts of wolfberry, 50 to 200 parts by weight of cornus oil
  • the pharmaceutical composition for lung cancer prevention or treatment characterized in that it comprises 50 to 200 parts by weight of bokbunja.
  • the composition preferably has an antioxidant activity
  • the extract is water, lower alcohol having 1-4 carbon atoms, acetone, ether, ethyl acetate, butyl acetate, chloroform, methylene chloride, hexane, 1,3 butylene glycol and It is preferable to extract with a solvent selected from the group consisting of these mixed solvents.
  • composition is Gobon, Cheonma, Shiho, Doin, Gyeji, Rhubarb, Licorice, Cheongung, Dermis, Taxa, Huangyan, Golden, Fuling, Peony, Baekchul, Hwangbaek, Gardenia, Banja, Jaguk, Jisil, Ginseng, Macmundong, Wonji , Seokchangpo, Creation, Gamkook, Windproof, Ginger, Forget-me-not, Contrast, dansam, Barberry, Chihwang, Mint, Potion, Spirit, Shouo, Guja, Absolute, Poisonous life, Tochung, Baekhwasaeng, Three hundred seconds, Injin, Jimo, Safflower, Astragalus, It may further include one or more herbal extracts selected from the group consisting of calendula, ginkgo biloba, yellow flower, lotus root, keel, phalanges, dew, sukji sulfur, black sesame
  • composition may be for the production of anticancer resonance stage.
  • Gun drug ( ⁇ ⁇ ) refers to a drug that can significantly enhance the therapeutic action for the etiology or main disease
  • new drug ( ⁇ ⁇ ) refers to a drug that enhances the therapeutic action in cooperation with military drugs.
  • Suppository ( ⁇ ⁇ ) is described in three meanings, first, drugs to treat humility or secondary symptoms, and second, to limit the toxic or weak order of military drugs ( ⁇ ⁇ ), and third, anti-left action ( ⁇ ⁇ ⁇ ), that is, to induce the throne by using drugs contrary to the weakness of the main medicine.
  • thermotropic drug for example, by applying a small amount of a thermotropic drug in a warming agent or by applying a relatively small amount of a thermosetting drug in a thermosetting agent, it is possible to reach the purpose of treatment because the heat of the heat is well received without resistance to each other.
  • two drugs having similar efficacy are combined to reinforce the original therapeutic effect.
  • the name is called constant, and the two drugs are different from each other.
  • the two different drugs are combined, the toxic reaction or side effect of one drug is suppressed by another drug, and the toxicity or efficacy
  • one drug may combine two drugs, one that reduces or eliminates the toxicity or side effects of the other.
  • one drug intervenes with another drug weakens or destroys the original properties and efficacy
  • the two drugs are combined, the toxic reactions or extreme side effects are applied to the therapeutic purpose of the disease.
  • the present invention is a method for observing the cell activity of the A549 human lung cancer cell line according to the basic principle of the Oriental medicine formula ( ⁇ ⁇ ⁇ ⁇ ; oriental medicine formula), Angelica gigantis radix, red ginseng, red turmeric ( turmeric (curcuma longa. L.)), tosa (cuscuta japonica) and Schizandra chinesis.
  • red ginseng and Schisandra chinensis effectively have liver cell protection
  • Angelica effectively reduces the cell activity of A549 human lung cancer cell line
  • earth and sand do not affect the cell activity of A549 human lung cancer cell line.
  • red ginseng corresponds to a group drug having a cell protective effect
  • a donkey corresponds to a renal drug having a cell killing effect
  • Schisandra chinensis has a cell protective effect.
  • Tosa and turmeric are four drugs. It does not appear to be fixed, but interacts with combinations and objects of action.
  • red ginseng and Schisandra chinensis had little effect on the cell survival rate of lung cancer cell lines, and the effects of earth and sand and turmeric are not significant, but donkey has a considerable effect (FIG. 1).
  • a significant decrease in cell viability was observed in the mixed administration of red ginseng, Angelica, Schisandra chinensis, Tosa and turmeric.
  • the fact that the cell survival rate in the red ginseng and donkey mixed treatment group was located in the middle of the experimental results of the red ginseng alone and donkey alone treatment group suggests that red ginseng protects the cells.
  • red ginseng which is a control drug, protects the cells
  • the donkey which is a new drug, kills lung cancer cells.
  • This can be said to be a suppository to help the role of the military.
  • This role-based interpretation focuses on reducing side effects rather than killing cells. This is an appropriate configuration considering the immunotherapy as an effort to reduce the situation in recent times and the cancer treatment is occurring side effects due to surgery, radiation therapy, chemotherapy, etc., but studies from various angles should be conducted. It is believed to be.
  • Red ginseng included in the composition of the present invention is a perennial herbaceous ginseng (Yang JP, Yeo IS: A study on the origins of 'Korean ginseng') belonging to the genus Araliaceae Panax ginseng . : 1-19) It is called red ginseng because the skin of red ginseng becomes red during the process of steaming 2-3 hours with water vapor for the purpose of long-term storage. .
  • red ginseng improves insulin sensitivity and attenuates the development of diabetes in Otsuka Long-Evans Tokushima fatty rats Metabolism. 2009; 58 (8): 1170-1177; Vuksan V, Sung MK, Sievenpiper JL, et al .: Korean red ginseng (Panax ginseng) improves glucose and insulin regulation in well-controlled, type 2 diabetes: results of a randomized, double-blind, placebo-controlled study of efficacy and safety.Nutr Metab Cardiovasc Dis.
  • Temper is sweet and bitter and has a flat nature and enters the nasal cavity and lungs. It is mainly used in Chinese medicine. It is used for sedation and excitability of the central nerve. It acts on the circulatory system to prevent hypertension or arteriosclerosis. It has the effect of cardiac action, antioxidant action, anti-fatigue, anti-radioactivity and hypoglycemic function.
  • the main ingredients are saponin (ginsenosides), panaxynol, beta-elemene and maltol.
  • the Angelica gigas Angelica gigas Nakai, a perennial herb belonging to the genus Arum ( Umbelliferae ), dried in the composition of the present invention is dried. Consists of essential oils and decousins, sedating beta sitosterol, sucrose, nicotinic acid and folic acid. Various women's diseases, menstrual disorders, menstrual cramps, anemia, poor uterine development, postpartum blood deficiency, menopausal disorders, etc. are effective throughout the female hormone secretion is effective. Recent studies have shown that donkeys have an excellent effect on cellular immune responses. In oriental medicine, it is warm in nature, sweet in taste, and works in the heart, liver and spleen. It replenishes and harmonizes the blood, regulates menstruation (menstruation), and helps stool well.
  • Schisandra chinensis is included in the composition of the present invention belong to the Schisandra schisandraceae (Schisandraceae) (North Schisandra) Schisandra chinensis Baill. Or Schisandra chinensis ( South Schisandra chinensis) S. sphenanthera Rehd . et Wils.'s ripe fruits are dried, containing about 3% essential oils, and various sesquicarene, ⁇ 2-bisabclene, ⁇ -chamigrene, and ⁇ -y GmbHe. The dried fruit contains 12% citral, 10% malic acid, and a small amount of tartaric acid, in addition to fructose, resin and the like. The nature is warm, flavored and sweet. It enters the lungs, heart and kidneys, converges and recollects, replenishes and produces essences, replenishes the energy of the kidneys and produces essences.
  • Earthenware is a mature seed of the same annual plant of Cuscuta chinensis LAM., C. japonica CHOISY, and C. australis R. BROWN. to dry (national college of Oriental Medicine, ed herbalism Seoul: Younglim four; 1994), a liver dysfunction recovery action (the myeongryeol, former lord: effects on liver function disorders of the tosaja extract experimentally induced rabbits J. Korean Soc. Food Nutr. 1989; 18 (3): 333-337), Anticancer Activity (Lee Bok Lee, Parallel: An Experimental Study on the Anticancer Activity and Immune Effect of Tosa Herbal Acupuncture. Journal of The Korean Acupuncture Society.
  • Curcuma Curcuma aromatica Salisb.
  • Curcuma Curcuma aromatica Salisb.
  • a perennial ripening herbaceous plant which is a turmeric root, turmeric, turmeric, and buds.
  • Antibiotic metabolism affects lipid metabolism (animal testing), which can reduce the formation of endothelial masses in the main and coronary arteries, reduce the deposition of lipids, and contain essential oils that promote bile secretion and excretion. It is known to be used for cholelithiasis because it has a dipharytic effect by contracting the gallbladder and dissolves filamentous stones.
  • the taste is spicy and bitter, and the nature is limited and nontoxic, and it promotes the circulation of the qi, loosening the loose, bleeding blood and removing the blood. It is known to treat thorax abdominal pain, vaginal embolism, fever newlyweds, hemorrhage, nasal bleeding, hematuria, hemorrhage, menstruation of men and jaundice.
  • goji berry, cornus and bokbunja can be used in addition to the immune-enhancing aspects, and the combination of red ginseng, donkey, schisandra chinensis, earth and sand, turmeric wolfberry, cornus and bokbunja extract is effective in terms of overall immunity in addition to the military affairs theory have.
  • the Gugija included in the compositions of the invention Solanaceae: Gugija tree belonging to the ( ⁇ Solanaceae) Lycium chinense Mill. Or other mature fruit of the same plant, mainly contains carotene, vitamin B1, vitamin B2, nicotin acid, vitamin C, ⁇ -sitosterol, linoleic acid and the like. According to the oriental medicine, the properties are flat, the taste is sweet, and it enters the liver and kidney to strengthen the function, supplement the tablets, and clear the eyes. Consistently taking it will reduce cholesterol and help prevent atherosclerosis. Its roots can also be used as a medicine, and pharmacological experiments of the root bark have shown that there is a drop in blood pressure, lowering blood sugar, and bactericidal action.
  • the cornus in the composition of the present invention is dried mature fruit of the cornus tree, which is a deciduous arborescent belonging to the dogwood ( ⁇ : ⁇ : Cornaceae ), the flesh of cornin, that is, verbenalin, saponin, tannin, ursolic acid and vitamin A
  • the seed oil contains palmitin acid, olein acid and linol acid.
  • Cornine a potent ingredient in the stomach, boosts metabolism and contains anti-diabetic substances.
  • cornus milk boosts the activity of immune cells, boosts immune function, and has some degree of anti-cancer effect.
  • oriental medicine the properties are warm, the taste is sour or steamed, and it acts on the liver and kidneys. Replenishes the function of the liver, kidneys and catches semen outflow.
  • Bokbunja contained in the composition of the present invention refers to less ripe fruit, that is, immature fruit of Rubus coreanus, a deciduous shrub of the Rosaceae family. Bokbunja has not only been used for food, but also as a medicinal herb for renal function, infertility, erosion, well-ventilation and jeongjeongje in oriental medicine and folk medicine. Bokbunja are known to have interpolation, nominal and diuretic effects. It was confirmed that the stem of Rubus Koreanum contained tannin components (-)-epicatechin, (+)-catechin and proanthocyanidins, and various flavonoid compounds were contained in the leaves.
  • Each herbal material included in the composition of the present invention may be used without limitation, such as cultivated or commercially available, and can be extracted or used as it is in a dry or natural state.
  • the herbal extracts of the present invention can be prepared using conventional methods known in the art, i.e., under conventional conditions of temperature and pressure, using conventional solvents.
  • Extractive solvents that may be used to prepare the herbal extracts of the present invention include, for example, water, lower alcohols having 1 to 4 carbon atoms, acetone, ether, ethyl acetate, butyl acetate, chloroform, methylene chloride, hexane and 1,3 butylene Extraction solvents, such as glycol, may be used alone or in combination, preferably methanol or ethanol, but is not limited thereto.
  • a suitable amount of the extraction solvent is about 1 to 20 times the dry weight of the herbal medicine, preferably 2 to 10 times.
  • the extraction method heat extraction, cold needle extraction, reflux cooling extraction, ultrasonic extraction, and the like may be used, and may be used by repeatedly extracting one or several times.
  • the extraction temperature and extraction time is not particularly limited as long as the temperature and time such that the effective activity of the useful ingredient of each herbal medicine is not removed.
  • the herbal extract of the present invention can be used by purification through a conventional purification process.
  • various purification methods additionally performed such as separation using an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity), etc. Fractions obtained through can be used.
  • the herbal extract of the present invention can be prepared and used in a powder state through a drying process such as distillation under reduced pressure, freeze drying and spray drying.
  • the pharmaceutical composition comprising the herbal extract of the present invention has antioxidant activity and exhibits anticancer effect on lung cancer.
  • the composition is characterized by containing a large amount of phenolic compound.
  • Phenolic compounds are one of the secondary metabolites widely distributed in the plant system and have various structures and molecular weights, and flavonoids and tannins are the main components.
  • Flavonoids are aromatic polyphenols and are broadly classified into flavonols, flavones, flavanones, flavanones, flavanols, anthocyanidins and isoflavones. . Because they have phenol hydroxyl (OH) groups, they easily bind to proteins and other macromolecules and have various physiological activities such as antioxidants and anticancer. Therefore, as the content of phenolic compound increases, antioxidant activity is enhanced.
  • the herbal extract of the present invention exhibits anticancer activity against lung cancer by inhibiting lung cell damage caused by oxidative stress.
  • the pharmaceutical composition of the present invention can be confirmed to inhibit lung cell damage by DEN (diethylnitrosamine) known as a carcinogen causing long-term damage by oxidative stress.
  • composition of the present invention may further include various other types of herbal extracts for enhancing the pharmacological anticancer effect of the herbal extracts, in addition to the herbal extracts of the red ginseng, goji berry, cornus oil, Schisandra chinensis, bokbunja, earth and sand, turmeric, and Angelica as active ingredients. have.
  • Herbal extracts that may be additionally included in the composition of the present invention include pharmaceutically acceptable herbal medicines, including Gobon, Cheonma, Shiho, Doin, Gyeji, Rhubarb, Licorice, Cheongung, Dermis, Taxa, Hulk, Golden, Bokyeong, Peony, Baekchul, Hwangbaek, Gardenia, Banja, Morning Light, Jisil, Ginseng, Macmun-dong, Wonji, Seokchangpo, Creation, Gamkook, Windproof, Ginger, Forget-me-not, Contrast, Sweet Ginseng, Barberry, Chihwang, Mint, Mountain Fertilizer, Spirit, Shou, Guja, Absolute, Poisonous life, tofu, baekryeoksaengcho, three hundred seconds, jinjin, jimo, safflower, Astragalus, calendula, ginkgo biloba, hwangjeong, lotus root, ke
  • the pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable carrier, and may be formulated with the carrier.
  • the 'pharmaceutically acceptable carrier' refers to a carrier or diluent that does not stimulate an organism and does not inhibit the biological activity and properties of the administered substance.
  • the composition may be prepared by filling the herbal extract with no excipient in the capsule or uniformly and sufficiently in contact with the atomized solid carrier, liquid carrier or both, and, if necessary, the product may be molded into a desired formulation.
  • suitable carrier excipients include starch, water, saline, ethanol, glycerol, Ringer's solution and dextrose solution, and the like (Remington's Pharmaceutical Science, 19 th Ed., 1995, Mack Publishing Company, Easton PA) and the like. As disclosed, it may be formulated into a suitable formulation known in the art.
  • composition of the present invention can be applied to any formulation containing it as an active ingredient, it can be prepared in oral or parenteral formulations.
  • Pharmaceutical formulations of the invention may be oral, rectal, nasal, topical (including the cheek and sublingual), subcutaneous, vaginal or parenteral (intramuscular, subcutaneous). And forms suitable for administration by inhalation or insufflation.
  • Oral dosage forms containing the composition of the present invention as an active ingredient include, for example, tablets, troches, lozenges, water-soluble or oily suspensions, preparation powders or granules, emulsions, hard or soft capsules, syrups or elixirs. can do.
  • lactose For formulation into tablets and capsules, lactose, saccharose, sorbitol, mannitol, starch, amylopectin, binders such as cellulose or gelatin, excipients such as dicalcium phosphate, disintegrants such as corn starch or sweet potato starch, stearic acid masne It may include a lubricating oil such as calcium, calcium stearate, sodium stearyl fumarate or polyethylene glycol wax, and in the case of a capsule, it may further contain a liquid carrier such as fatty oil in addition to the above-mentioned materials.
  • a lubricating oil such as calcium, calcium stearate, sodium stearyl fumarate or polyethylene glycol wax
  • a liquid carrier such as fatty oil in addition to the above-mentioned materials.
  • Formulations for parenteral administration comprising the composition of the present invention as an active ingredient include injectables, creams, lotions, external ointments, oils, moisturizers, gels, aerosols and nasal inhalants in the form known in the art.
  • Can be mad. Specifically, it may be formulated for injection such as subcutaneous injection, intravenous injection or intramuscular injection, suppository injection method or aerosol for inhalation through respiratory system.
  • the compositions of the present invention may be mixed in water with stabilizers or buffers to prepare solutions or suspensions, which may be formulated for unit administration of ampoules or vials.
  • suppositories For infusion into suppositories, it may be formulated as a rectal composition such as suppositories or body enema including conventional suppository bases such as cocoa butter or other glycerides.
  • a propellant or the like When formulated for spraying such as aerosols, a propellant or the like may be combined with the additives to disperse the dispersed dispersion or wet powder.
  • the pharmaceutical composition of the present invention comprises arithmetic and Angelica known as the main constituents of the resonant stage, which is a representative herbal medicine, and contains other herbal medicines, that is, red ginseng, wolfberry, Schisandra chinensis, bokbunja, earthenware and turmeric in an appropriate amount, Since it exhibits anti-cancer activity, it can be used for the production of anti-cancer resonators for preventing or treating lung cancer. Therefore, the composition of the present invention is particularly preferably processed in the form of pills.
  • the pill form is concentrated by extracting the herbal medicine and then finely pulverizing each medicine by using a grinder to mix the extract and powder, and put the powder mixed with the chemical liquid again into a grinder to filter the fine particles 300-500mesh sieve fine particles
  • Herbs made of round, sweet and round can be packaged again using edible gold leaf (or silver leaf).
  • Gold or silver has long been used in making pills to stabilize the mind and have been used as an auxiliary material in prescriptions such as resonant stages and cow sulfur cheongsimwon with the effect of insect repellent protection.
  • the process of making the ring in the other form is the same, and has been used as a dye from herbal medicines such as porcelain and salvia and has been used as a dye from the past, and can be used by coating the surface to extract the effective insect repellent.
  • the lung cancer prevention or treatment method of the present invention is characterized in that it comprises administering the pharmaceutical composition.
  • the term "administration" means introducing a pharmaceutical composition of the present invention to a patient in any suitable manner, and the route of administration of the composition of the present invention may be various oral or parenteral routes as long as it can reach the desired tissue. It may be administered through, or specifically, can be administered in a conventional manner via oral, rectal, topical, intravenous, intraperitoneal, intramuscular, intraarterial, transdermal, nasal, inhalation, intraocular or intradermal route. . Preferably oral administration.
  • the treatment method of the present invention comprises administering a composition containing the herbal extract in a pharmaceutically effective amount. It will be apparent to those skilled in the art that a suitable total daily dose may be determined by the practitioner within the correct medical judgment and may be administered to the patient in a single dose and in multiple doses. Administration may be by long-term, fractionated treatment protocols.
  • the specific therapeutically effective amount for a particular patient may be based on the specific composition, including the type and severity of the reaction to be achieved, whether or not other agents are used in some cases, the age, weight, general health, sex and diet of the patient, time of administration, It is desirable to apply differently depending on the route of administration and the rate of release of the composition, the duration of treatment, and the various factors and similar factors well known in the medical arts, including drugs used with or concurrent with the specific composition. Therefore, the effective amount of a pharmaceutical composition suitable for the purpose of the present invention is preferably determined in consideration of the above matters. However, for the desired effect, the compound of the present invention may be administered in an amount of 0.0001 to 100 mg / kg, preferably 0.01 to 10 mg / kg, divided once to several times daily.
  • the method for preventing or treating lung cancer of the present invention is applicable to any animal in which lung cancer may occur, and animals include humans and primates, as well as domestic animals such as cattle, pigs, sheep, horses, dogs, and cats. .
  • composition of the present invention can be used alone or in combination with methods using surgery, hormone therapy, drug treatment and biological response modifiers for the treatment of lung cancer.
  • the present invention provides a composition for preventing or improving lung cancer comprising the extract of Angelica tang as an active ingredient.
  • the composition preferably comprises extracts of red ginseng, goji berry, cornus oil, Schisandra chinensis, bokbunja, earth and sand, turmeric, and Angelica as active ingredients.
  • composition of the present invention may be added to a dietary supplement for the purpose of preventing or improving lung cancer.
  • each herbal material included in the composition may be used in a manner of additionally adding the powder itself in addition to the extract form.
  • the health functional food may be prepared by adding other food materials according to the commerciality and consumer preference of the final product.
  • the effective amount of the composition can be suitably determined according to the purpose of use (prevention, health or therapeutic treatment), preferably 0.001 to 90% by weight, more preferably 5 to 5, based on the dry weight of the herbal medicine relative to the total raw material. It can be added at 30% by weight.
  • the pharmaceutical composition of the present invention can be prepared as a health functional food in the form of a preparation by further comprising a food additive acceptable food formulation, the form of the preparation can be tablets, capsules, pills, liquids and the like. .
  • beverages including alcoholic beverages
  • fruits and processed foods e.g. canned fruit, canned foods, jams, marmalade, etc.
  • fish meat and processed foods
  • meat and processed foods e.g. ham, sausage cornebi, etc.
  • Breads and noodles e.g. udon, soba, ramen, spaghetti, macaroni, etc.
  • fruit juices various drinks, cookies, malts, dairy products (e.g.
  • the health functional food of the present invention is a variety of flavors, natural carbohydrates, sweeteners, vitamins, electrolytes, colorants, pectic acid, alginic acid, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols, carbonating agents And the like may be further contained.
  • the natural carbohydrate may be a sugar such as glucose, monosaccharides such as fructose, maltose, disaccharides such as sucrose, polysaccharides such as dextrin, cyclodextrin, xylitol, sorbitol, and erythritol.
  • sweetener natural sweeteners such as tautin and stevia extract, synthetic sweeteners such as saccharin, aspartame, and the like can be used.
  • the ratio of such additives is not critical but may be selected in the range of 0.01 to 10 g per 100 ml of the composition of the present invention.
  • the pharmaceutical composition for preventing or treating lung cancer of the present invention has an antioxidant activity and exhibits an anticancer effect through inhibiting lung cell damage by oxidative stress, and thus, a pharmaceutical agent for treating or preventing lung cancer and It can be usefully used in the manufacture of dietary supplements.
  • the pharmaceutical composition is excellent in texture when processed in the form of pills can be used in the manufacture of anti-cancer diagnostics for the treatment or prevention of lung cancer.
  • the combination of the present invention is more significant in terms of military history and overall immunity.
  • FIG. 1 is a graph showing the effects of the single ethanol extract of each of the herbal medicines constituting the drug on the cell activity of the A549 human lung cancer cell line (A: red ginseng, B: Angelica, C: Schisandra chinensis, D: earthworm, E: turmeric)
  • A red ginseng, B: Angelica, C: Schisandra chinensis, D: earthworm, E: turmeric
  • the data represents the mean ⁇ standard deviation of the results of three repeated experiments.
  • FIG. 2 is a graph showing the effects of the ethanol extracts of the herbal extracts of the herbal medicines on the cell activity of the A549 human lung cancer cell line (A: red ginseng + Angelica, B: red ginseng + Schisandra chinensis, C: Angelica + turmeric, D: red ginseng) + Donkey + turmeric, E: donkey + earthworm + turmeric, F: red ginseng + donkey + earthworm + turmeric, G: red ginseng + donkey + Schisandra + sesame seed + turmeric), and the data shows the mean ⁇ standard deviation of three replicates. Indicates.
  • Figure 4 illustrates a series of procedures for obtaining methanol, hexane, chloroform, ethyl acetate, butanol and aqueous layer fractions of herbal extracts according to the present invention.
  • Figure 6 is a graph measuring the measurement of SOD (Superoxide dismutase) -like activity of the herbal extract according to the present invention.
  • 7 and 8 are the results of the investigation of the shape of the lung tissue after administering the herbal extract according to the present invention to the lung cancer induced rats.
  • FIG. 9 is a graph evaluating the effect of the herbal extracts according to the present invention on LDH activity of lung cancer induced rats.
  • FIG. 10 is a graph evaluating the extent of inhibition of proliferation of A549 cells, the herbal extracts of the present invention are lung cancer cell lines.
  • the present inventors made powders of red ginseng (Ganghwado, 6 years old), donkey, schisandra chinensis, earth and sand, Ulgeum (hereinafter, Omni Herb, Korea), which were verified in the main school of Woosuk University, and then eluted by cooling them in 100% ethanol for 3 days.
  • the extract was concentrated under reduced pressure and freeze dried. These were each dissolved in DMSO and stored frozen until use.
  • A549 human lung cancer cell line was used by the National Cancer Center.
  • the lung cancer cell lines were cultured in RPMI1640 culture medium containing 10% FBS and penicillin, streptomycin, 25 mM HEPES, 1 mM sodium pyruvate.
  • each well was dispensed with A549 human lung cancer cell lines (1.6 X 10 3 cells) per 96 well plate and cultured. After 24 hours, each extract of the culture solution was diluted to a predetermined concentration and injected into each well. After 48 hours of further incubation, the viability of the cells was confirmed with PrestoBlue (Invitrogen) reagent.
  • PrestoBlue Invitrogen
  • red ginseng 6-year-old ethanol extract in Ganghwa-do on cell viability of lung cancer cell line (A549) at various concentrations showed that red ginseng ethanol extract did not directly affect lung cancer cell survival rate.
  • concentration of red ginseng ethanol extract observed in the experiment was observed from about 160 mg / ml to 5 mg / ml, and even at a concentration of 160 mg / ml, more than 100% cell viability was observed (FIG. 1A).
  • the effect of ethanol extract of Angelica gigas from Omnihub Co., Ltd. on cell viability of lung cancer cell line (A549) was examined at various concentrations.
  • the cell survival rate of about 89.0% was observed at 31.3 mg / ml of Angelica gigas ethanol extract, and the cell survival rate of about 56.5% at 62.5 mg / ml was observed to suppress the survival of lung cancer cell lines (FIG. 1B).
  • the cell survival rates of the lung cancer cell lines were as follows. When the cell viability at the M1 concentration of the untreated group was converted to 100.0%, the cell viability at the M2 concentration was about 105.7%, the cell viability at the M3 concentration was about 110.0%, the cell viability at the M4 concentration was about 104.5%, The cell viability at M5 concentration was about 94.2%, the cell viability at M6 concentration was about 80.8%, and the cell viability at M7 concentration was about 48.9% (Fig. 2C).
  • the effects of red ginseng and the concentration of donkey and turmeric on the cell survival rate of lung cancer cell lines were as follows.
  • the cell viability at M2 concentration was about 109.6%
  • the cell viability at M3 concentration was about 112.8%
  • the cell viability at M4 concentration was 104.5%
  • the cell viability at M5 concentration was about 94.0%
  • the cell viability at M6 concentration was Cell viability at about 78.3% and M7 concentration was observed at about 45.5% (FIG. 2D).
  • the effects of the combination of donkey, earth and sand and turmeric on the cell survival rate of lung cancer cell lines were as follows.
  • the cell viability at the M1 concentration of the untreated group was 100.0%
  • the cell viability at the M2 concentration was about 106.9%
  • the cell viability at the M3 concentration was about 101.3%
  • the cell viability at the M4 concentration was about 104.2%
  • the cell viability at M5 concentration was about 97.4%
  • the cell viability at M6 concentration was about 78.7%
  • the cell viability at M7 concentration was about 44.8% (FIG. 2E).
  • the effects of red ginseng, Angelica, sediment, and turmeric on the cell survival rate of lung cancer cell lines were as follows.
  • the cell viability at the M1 concentration of the untreated group was converted to 100.0%
  • the cell viability at the M2 concentration was about 108.2%
  • the cell viability at the M3 concentration was about 111.8%
  • the cell viability at the M4 concentration was about 100.0%
  • Cell viability at M5 concentration was about 108.1%
  • cell viability at M6 concentration was about 76.8%
  • cell viability at M7 concentration was about 41.2% (FIG. 2F).
  • the effects of red ginseng, Angelica, Schisandra chinensis, Tosa and turmeric on the cell survival rate of lung cancer cell lines were as follows.
  • the cell viability at the M1 concentration of the untreated group was converted to 100.0%
  • the cell viability at the M2 concentration was about 95.1%
  • the cell viability at the M3 concentration was about 92.9%
  • the cell viability at the M4 concentration was about 86.6%
  • the cell viability at M5 concentration was about 86.4%
  • the cell viability at M6 concentration was about 62.9%
  • the cell viability at M7 concentration was about 35.7% (FIG. 2G).
  • red ginseng, wolfberry, cornus oil, Schisandra chinensis, bokbunja, earth and sand, turmeric and Angelica were purchased and then ground.
  • the powdered herbal medicines were made to have a total herbal weight of 1 kg in the composition of Table 2, and then extracted with 4 L of 100% methanol at 70 ° C. for 3 hours using an extractor to prepare a herbal extract.
  • the 100% methanol extract prepared in the above ⁇ 4-1> process was prepared in five fractions by separating the polar solvent from the nonpolar solvent in the order of polar solvent using the polarity difference of the solvent in the same manner as in FIG. 4.
  • the methanol extract was concentrated under reduced pressure, n-hexane and water were mixed and dissolved in the separatory funnel to obtain an n-hexane fraction layer.
  • the aqueous layer was placed in a separatory funnel, and chloroform, ethyl acetate, n-butanol and aqueous fractions were sequentially obtained in the same manner.
  • the methanol extract, the hexane fraction, the chloroform fraction, the ethyl acetate fraction, the butanol fraction, and the extract of the aqueous layer were then concentrated under reduced pressure, lyophilized, and the yield of each fraction was determined by gravimetric method.
  • Each fraction extract was stored frozen at -70 °C was used in the experiment.
  • the herbal extract thus obtained was named 'anticancer diagnostic diagnosis extract'.
  • Age rats (Rat, Sprague Dawley) of about 180 ⁇ 10 g body weight were purchased from Samtaco (Osan, Korea). The experimental animals were supplied with sufficient solid food (for cryingaco, rats) and water under certain conditions (temperature: 21 ⁇ 2 °C, humidity: 50-60%, 12 hours light / dark cycle) in the animal breeding room of Wonkwang University. Adapted for 1 week while being used in the experiment.
  • oxidative stress The formation and development of cancer by oxidative stress is well known.
  • the main mechanism of DEN stimulation a carcinogen, is in inducing oxidative stress. Therefore, the present inventors confirmed the degree of oxidative stress inhibition to determine whether the herbal extracts can inhibit oxidative stress.
  • ABST method is the most frequently used method of indirect one of the antioxidant capacity measurement method.
  • Antioxidant activity was measured using ABTS radicals by removing the ABTS free radicals produced by the reaction with potassium persulfate by the antioxidants in the sample and decolorizing the cyan color which is specific to radicals. Measured. Specifically, 7 mM 2.2-azino-bis (3-rthylbenzthiazoline-6-sulfonic acid) (ABTS) and 2.45 mM potassium persulfate were mixed at the final concentration for 24 hours in a cow at room temperature to form ABTS + radical. Diluted with distilled water at 0.9 nm so that the absorbance value is 0.9 ( ⁇ 0.1).
  • ABST antioxidant capacity of the methanol extract was observed to be about 81.17 ⁇ 0.36%
  • chloroform fraction showed an antioxidant capacity of 72.40 ⁇ 0.24%
  • Ethyl acetate fraction showed the lowest ABST antioxidant activity of about 65.13 ⁇ 0.14%
  • n-hexan fraction showed the highest ABST antioxidant activity of 92.68 ⁇ 0.24%.
  • the total polyphenol content of the herbal extracts was analyzed based on the principle that the Folin-ciacalteu rearent was colored by molybdenum blue as a result of reduction by the polyphenol compound of the anticancer resonance group according to the method of Dewanto10).
  • To 100 ⁇ l of herbal extracts (methanol extract, chloroform fraction, ethanol fraction and hexane fraction) of each fraction add 100 ⁇ l of Folin-Ciocalteau's phenol regent, mix, hold for 3 minutes at room temperature, and add 100 ⁇ l of 2% Na 2 CO 3 solution. After mixing, the mixture was left at room temperature for 1 hour and the absorbance was measured at 750 nm.
  • Example ⁇ 4-1> In order to compare the extraction efficiency according to the solvent, the extract extracting the herbal medicine with distilled water instead of methanol in Example ⁇ 4-1> was experimented together.
  • gallic acid a standard substance, was dissolved in distilled water, and prepared according to a certain concentration, and the experiment was performed in the same manner as the sample to prepare a calibration curve and to measure the total phenol content of the sample. The results are shown in Table 3 below. It was.
  • the total phenolic content of the herbal extract was 1.19 ⁇ 0.03 mg / g
  • the total phenolic content of the methanol extract was about 1.19 ⁇ 0.01 mg / g.
  • the chloroform fraction showed a total phenolic content of 1.05 ⁇ 0.01 mg / g
  • the ethyl acetate fraction had a total phenolic content of about 1.17 ⁇ 0.01 mg / g
  • the n-hexan fraction had the highest total content of 1.32 ⁇ 0.01 mg / g.
  • Total phenolic content is shown.
  • the total flavonoid content of the herbal extract was 27.87 ⁇ 1.23 mg / g, and the total flavonoid content of the methanol extract was about 32.80 ⁇ 1.07 mg / g.
  • the chloroform fraction showed a total phenolic content of 30.69 ⁇ 0.72 mg / g, the ethyl acetate fraction had a total flavonoid content of about 14.09 ⁇ 0.54 mg / g, and the n-hexan fraction had a total flavonoid of 21.62 ⁇ 0.59 mg / g. Content is indicated.
  • SOD is known as an enzyme that can suppress aging by reducing superoxide to normal oxygen and various diseases such as cancer involving superoxide.
  • SOD-like activity pyrogallol is automatically oxidized by superoxide radicals in water to form a brown substance, which is analyzed by spectrophotometer, and the oxidation rate of pyrogallol is lowered in the presence of a substance having superoxide trapping activity.
  • Superoxide capture activity can be measured indirectly.
  • SOD-like activity was measured according to Markund et al.
  • Tris-HCl buffer 50 mM tris amino-methane and 10 mM EDTA adjusted to pH 8.5 in 0.2 ml (1 mg / ml concentration) of herbal extracts (methanol extract, chloroform fraction, ethanol fraction and hexane fraction) of each fraction 2.6
  • herbal extracts methanol extract, chloroform fraction, ethanol fraction and hexane fraction
  • the amount of oxidized pyrogallol in the reaction solution was measured for absorbance at 420 nm. SOD-like activity measurement was calculated by the following equation 2, the results are shown in FIG.
  • the SOD-like activity of the methanol extract was observed to be about 20.93 ⁇ 0.91%, the chloroform fraction showed a SOD-like activity of 7.67 0.31%.
  • Ethyl acetate fraction showed SOD-like activity at 26.52 ⁇ 0.61% and n-hexan fraction showed SOD-like activity at 26.52 ⁇ 3.15%.
  • the herbal extracts were stimulated with DEN in the rat prepared in Example ⁇ 4-3> to induce renal cell carcinoma, and then examined the effects on lung tissue.
  • lung cancer induction was performed as follows.
  • the experimental group was divided into three groups of five by the ingot method, divided into normal group (group 1), control group (DEN injection, group 2), dietary intake group (DEN + anticancer diagnostic methanol extract, group 3).
  • group 1 normal group
  • control group DEN injection, group 2
  • dietary intake group DEN + anticancer diagnostic methanol extract, group 3
  • group 3 dietary intake group
  • the dietary intake group (group 3) dissolved the conventional feed and ethanol extract of anticancer resonance diagnostic agent of 150 ppm + 100 mg / kg DEN and supplied it as a negative.
  • lung tissue was obtained from five rats of each group, Histology a text and Atlas. Michael H. Ross, Wojciech Pawlina. Kim Jin-jung and five others. Color histology walk.
  • the shape of lung tissue was investigated by referring to the method described in [Korea Medicine]. Specifically, the obtained lung tissue was fixed with NBF solution, and then paraffin embedding was performed to prepare tissue sections of 5 ⁇ m thickness using a microtome, followed by hematoxylin & eosin (H-E) staining. Lung tissue was observed under a microscope (X20 ⁇ , X40 ⁇ ) using a specimen having 100 fields or more, and the results are shown in FIGS. 7 and 8.
  • alveoli in lung tissue are surrounded and separated from each other by a thin layer of connective tissue, ie, interalveolar septum.
  • the connective tissue layer is thin and sparse, but in the control group in which lung cancer is induced, the connective tissue layer is thick and the alveoli are also smaller than the normal group.
  • the connective tissues were thicker than the normal group, but clearly thinner than the control group. The experimental group was able to confirm that the number of alveoli and alveolar sacs also maintained a constant shape compared to the control group.
  • the lung cancer-induced control group has been observed more microvascular and red blood cells than the normal group.
  • the density of the lungs in the control group can be confirmed that more dense than the normal group.
  • the experimental group fed the chemodiagnosis group can confirm that the lung density is not as dense as the control group and is almost similar to the normal state. That is, the herbal extract can be seen that the lung tissue has a protective effect against DEN stimulation.
  • LDH activity in serum was evaluated.
  • LDH lactate dehydrogenase
  • lung cancer induction was performed in the same manner as in Example 6.
  • the experimental group was divided into three groups of five by the ingot method, divided into normal group (group 1), control group (DEN injection, group 2), dietary intake experimental group (DEN + anticancer diagnostic methanol extract, group 3).
  • group 1 normal group
  • control group DEN injection, group 2
  • dietary intake experimental group DEN + anticancer diagnostic methanol extract, group 3
  • the control group was administered with 150 ppm of DEN in a negative form for 12 weeks.
  • the experimental group (group 3) dissolved the normal feed and DEN 150ppm + 100 mg / kg GJD was supplied as a negative.
  • rats were anesthetized with urethane, and then dissected along the midline of the abdomen and ascended intravenous bleeding.
  • the blood was placed in a test tube and allowed to stand at room temperature for 30 minutes to coagulate the blood, and then centrifuged at 3000 rpm, and the supernatant was recovered and stored in a -80 ° C. cryogenic freezer for use in experiments.
  • LDH activity was measured using a kit reagent for autoanalyzer (Dong-Pharma Pharmaceutical), and the results are shown in FIG. 9.
  • the LDH activity was significantly increased in the control group compared to the normal group, and in the experimental group coadministered with the herbal extract was significantly reduced compared to the control group was observed.
  • the effect of the herbal extracts on the degree of proliferation of lung cancer cells was evaluated.
  • the degree of proliferation was measured using a known MTT assay method (FIG. 10).
  • the MTT assay is a method of measuring the amount of dark blue formazan produced by MTT by the action of oxide-reductase in the mitochondrial lining of living cells.
  • the production of dark blue formazan is known to be nearly proportional to the number of living cells that are metabolically active, which is very effective in measuring cell growth and differentiation.

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Abstract

La présente invention concerne une composition pharmaceutique comprenant un extrait de plantes médicinales pour la prévention ou le traitement du cancer du poumon. Elle concerne plus particulièrement une composition pharmaceutique comprenant un extrait de ginseng rouge, d'Angelica gigas, de schizandra, de Semen cuscutae et de curcuma, utilisé comme ingrédient actif pour la prévention ou le traitement du cancer du poumon. Cette composition pharmaceutique, qui présente une activité antioxydante élevée, est particulièrement efficace dans la prévention du cancer du poumon.
PCT/KR2011/007676 2010-10-14 2011-10-14 Composition pharmaceutique comprenant un extrait de plantes médicinales pour la prévention ou le traitement du cancer du poumon WO2012050398A2 (fr)

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CN116531465A (zh) * 2023-06-20 2023-08-04 陈向群 一种治疗肿瘤和/或肺结节的中药方剂及其制备方法

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CN102645364A (zh) * 2012-05-03 2012-08-22 沈阳药科大学 泽泻致肾毒性作用毒效部位及其制备方法
CN103127296A (zh) * 2013-03-18 2013-06-05 江苏省中医药研究院 一种具有肺癌化疗增效减毒作用的中药组合物及其制备方法和应用
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CN104383446A (zh) * 2014-11-30 2015-03-04 顾蔷怡 一种治疗脾胃虚寒症的药物及其制备方法
CN113287706A (zh) * 2021-05-10 2021-08-24 郭建斌 一种木参牡蛎速溶保健颗粒及其制备方法
CN116531465A (zh) * 2023-06-20 2023-08-04 陈向群 一种治疗肿瘤和/或肺结节的中药方剂及其制备方法

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