WO2022097794A1 - Composition pour la prévention ou le traitement de la cachexie, contenant un extrait complexe de salviae miltiorrhizae radix et de rhei radix et rhizoma - Google Patents

Composition pour la prévention ou le traitement de la cachexie, contenant un extrait complexe de salviae miltiorrhizae radix et de rhei radix et rhizoma Download PDF

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WO2022097794A1
WO2022097794A1 PCT/KR2020/015608 KR2020015608W WO2022097794A1 WO 2022097794 A1 WO2022097794 A1 WO 2022097794A1 KR 2020015608 W KR2020015608 W KR 2020015608W WO 2022097794 A1 WO2022097794 A1 WO 2022097794A1
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cancer
cachexia
composition
preventing
complex extract
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PCT/KR2020/015608
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Korean (ko)
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엄재영
안광석
이석근
양웅모
정윤우
박진봉
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경희대학교 산학협력단
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Priority to PCT/KR2020/015608 priority Critical patent/WO2022097794A1/fr
Priority to JP2023527759A priority patent/JP2023548411A/ja
Publication of WO2022097794A1 publication Critical patent/WO2022097794A1/fr

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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
    • 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)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/537—Salvia (sage)
    • 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)
    • A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a composition for preventing, improving or treating cachexia comprising a herbal medicine complex extract, and more particularly, to prevent and improve cancerous cachexia comprising a complex extract of Salviae Miltiorrhizae Radix and rhubarb (Rhei Radix et Rhizoma). Or it relates to a pharmaceutical composition for treatment, a health functional food composition, and an anticancer adjuvant composition.
  • Cachexia refers to a complex syndrome that causes persistent muscle loss caused by various diseases such as cancer, heart failure, chronic obstructive pulmonary disease, chronic kidney disease, AIDS, and the like.
  • cancer cachexia is a complex metabolic syndrome accompanied by malignant tumors, and is defined as a loss of more than 5% in body weight due to muscle and fat loss within 6 months of the onset of cancer.
  • Cachexia can occur in a variety of medical conditions, but cancerous cachexia is closely related to terminal cancer. About 50% of all cancer patients, particularly about 80% of those with terminal cancer, are affected by cancerous cachexia and suffer from reduced life and increased mortality due to loss of muscle and/or fat.
  • Cancer cachexia is characterized by weight loss through significant loss of muscle mass and/or adipose tissue, and has a different characteristic than muscle and fat loss through appetite suppression.
  • Treatments for cancer cachexia include NSAIDs (non-steroidal anti-inflammatory drugs), ⁇ 2-adrenergic agonists, corticosteroids, and ghrelin. There are ⁇ inhibitors.
  • a COX-2 inhibitor is a drug that reduces the loss of skeletal muscle by inhibiting COX-2, which is involved in the production of prostaglandins, which are inflammatory substances generated in large amounts in cancer tissues.
  • COX-2 inhibitor As a COX-2 inhibitor, celecoxib is commercially available. However, side effects such as anemia, gastric ulcer, allergy, heart attack and stroke have been reported with celecoxib.
  • a TNF- ⁇ inhibitor is a drug that kills cancer cells by reducing the expression of TNF- ⁇ , which is often expressed in the bloodstream of patients with cancer cachexia.
  • Thalidomide is commercially available as a TNF- ⁇ inhibitor.
  • these drugs have little effect as a treatment for cancer cachexia, and have side effects such as depression, heart failure, shortness of breath, vomiting, rash, high blood pressure, and birth defects during pregnancy.
  • Salviae Miltiorrhizae Radix is an herbal medicine derived from the root of Salvia miltiorrhiza Bunge belonging to the Lamiaceae family. It has shown activity on osteoporosis, central nervous system action, anti-inflammatory, antioxidant, and anticancer action.
  • Rhubarb (Rhei Radix et Rhizoma) is the root and rhizome of Rheum palmatum Linne, Rheum tanguticum Maximowicz ex Balf., or medicinal rhubarb ( Rheum officinale Baillon), which are perennial herbs belonging to the Polygonaceae family. It is clinically applied to the treatment of indigestion, constipation, acute inflammation, infectious disease, parasitic disease, bleeding, thrombocytopenia, burns and skin diseases.
  • the present inventors found that the complex extract of ginseng and rhubarb, a natural product, suppresses weight loss and fat loss due to cancer in an animal model of obesity/cancer comorbidity, induces cancer cell death, and has significant anticancer and cancer cachexia improvement effects. By confirming, the present invention was completed.
  • Another object of the present invention is to provide a health functional food composition and health food composition for preventing or improving cachexia.
  • Another object of the present invention is to provide an anticancer adjuvant composition comprising the pharmaceutical composition.
  • Another object of the present invention is to provide a method for preventing or treating cachexia.
  • the present invention provides a pharmaceutical composition for preventing or treating cachexia comprising a complex extract of Salviae Miltiorrhizae Radix and Rhubarb (Rhei Radix et Rhizoma).
  • the cachexia may be caused by cancer.
  • the present invention provides a health functional food composition and health food composition for preventing or improving cachexia comprising a complex extract of ginseng and rhubarb.
  • the present invention provides an anti-cancer adjuvant composition comprising the pharmaceutical composition for preventing or treating cachexia.
  • the present invention provides a method for preventing or treating cachexia comprising administering to a patient the pharmaceutical composition for preventing or treating cachexia.
  • the complex extract of dandelion ginseng and rhubarb of the present invention suppresses weight loss and fat loss due to cancer in an animal model of obesity/cancer comorbidity, and induces cancer cell death through caspase cascade activation, thereby significantly improving anticancer and cancer cachexia Therefore, it may be useful as a composition for preventing, improving or treating cancerous cachexia, which can simultaneously improve anticancer treatment and cachexia without cachexia side effects.
  • body weight change is a body weight change (body weight change), cancer tissue weight (tumor weight) of the animal model of obesity / cancer comorbidity according to the treatment of the complex extract of ginseng and rhubarb of the present invention, the weight of the cancer tissue in the total weight of the rat
  • body weight cancer free body weight
  • subcutaneous fat is inguinal white adipose tissue, iWAT
  • visceral fat epididymal white adipose tissue, eWAT
  • Figure 2 shows the effect on the expression of cancer cell death-related factors (Bcl-xl, Bax, cleaved-caspase 3 and caspase 3) of the complex extract of dandelion and rhubarb.
  • the present invention provides a pharmaceutical composition for preventing or treating cachexia comprising a complex extract of Salviae Miltiorrhizae Radix and Rhubarb (Rhei Radix et Rhizoma).
  • the term 'cachexia' refers to a high degree of general weakness that can be seen in the late stages of cancer, tuberculosis, diabetes, acquired immunodeficiency syndrome, AIDS, etc., and gastric cancer, esophageal cancer, pancreatic cancer It is frequently seen in patients with gastrointestinal cancer such as colon cancer and lung cancer. It shows symptoms such as decreased appetite, decreased body weight and stamina due to muscle and fat reduction, anemia, lethargy, indigestion, and the like. When cachexia develops, it shows a low response to chemotherapy or radiation therapy, which reduces the patient's quality of life, shortens life expectancy, and causes death due to weight loss in 10 to 20% of all cancer patients. do.
  • the cachexia may be caused by cancer.
  • cachexia induced by the cancer is expressed as 'cancer cachexia'.
  • the pharmaceutical composition according to the present invention may be to improve one or more symptoms selected from the group consisting of decreased appetite, weight loss, increased fatigue, increased inflammation, muscle loss, fat loss, and hematopoietic toxicity, preferably body weight It may be to improve one or more symptoms selected from the group consisting of reduction and fat loss.
  • the pharmaceutical composition according to the present invention may simultaneously exhibit an anticancer effect and a cancerous cachexia inhibitory effect.
  • the anticancer effect may be shown through activation of one or more factors selected from the group consisting of Bax and caspase 3.
  • it may be one that exhibits a cancer cell death effect by caspase cascade activation.
  • the complex extract of ginseng and rhubarb showed an effect of improving weight loss and fat loss due to cancer tissue in an animal model of obesity/cancer comorbidity, and Bax and By showing the effect of activating the expression of caspase3 and the effect of inhibiting cancer, the effect of improving the cancer cachexia as well as the anticancer effect was confirmed (see Experimental Examples 1 to 3).
  • the above effect may be that the effect of the complex extract of ginseng and rhubarb of the present invention is significantly increased compared to each single extract.
  • the complex extract of dandelion ginseng and rhubarb may be a mixture obtained by extracting a mixture of dandelion ginseng and rhubarb, and may be a mixture of extracts obtained by extracting each extract of dandelion ginseng and rhubarb, but is not limited thereto.
  • extract refers to a preparation concentrated by squeezing the extraction target with an appropriate leachate and evaporating the leachate, but is not limited thereto, but is not limited thereto, It may be a dried product obtained, a crude product or a purified product thereof.
  • the extraction method is not limited thereto, but preferably, methods such as hot water extraction, hot water extraction, cold extraction, reflux cooling extraction, or ultrasonic extraction may be used.
  • the complex extract is mixed with ginseng and rhubarb; and immersing the mixture in water, C1 to C4 alcohol, ethyl acetate, or a mixture thereof to obtain an extract; may be prepared by a method comprising, but is not limited thereto.
  • the C1 to C4 alcohol may be ethanol, methanol, butanol, or a combination thereof.
  • Extraction may be performed by adding the extraction solvent in an amount of 1 to 10 times the weight of the mixture of dandelion and rhubarb.
  • the extraction temperature may be 30 to 120 °C, but is not limited thereto.
  • the extraction time may be 2 to 48 hours, but is not limited thereto.
  • the ginseng and rhubarb may be mixed in a weight ratio of 0.1:10 to 10:0.1, preferably mixed in a weight ratio of 0.5:5 to 5:0.5, more preferably 1:3 to 3: It may be mixed in a weight ratio of 1, and mixing in a weight ratio of 1:2 to 2:1 may be the most preferable.
  • the extraction method may further include fractionating the extract with water, C1 to C4 alcohol, or a combination thereof. Preferably, it may be fractionated with water, ethanol, methanol, butanol, ethyl acetate, hexane, or a combination thereof.
  • the extraction method may further include performing concentration, centrifugation, filtration, adsorption, or chromatography on the extract.
  • the pharmaceutical composition according to the present invention may be formulated for oral administration, intramuscular administration, intravenous administration, intraperitoneal administration, subcutaneous administration, intradermal administration, or topical administration.
  • the complex extract of dandelion ginseng and rhubarb of the present invention can be administered in various oral and parenteral formulations during clinical administration. or using an excipient.
  • Solid preparations for oral administration include tablets, patients, powders, granules, capsules, troches, and the like, and these solid preparations include at least one or more excipients, such as starch , calcium carbonate, sucrose, lactose, or gelatin is mixed and prepared. In addition to simple excipients, lubricants such as magnesium stearate talc are also used.
  • Liquid formulations for oral administration include suspensions, solutions, emulsions, or syrups. In addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. can
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspension solutions, emulsions, lyophilized formulations, suppositories, and the like.
  • Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.
  • injectable esters such as ethyl oleate.
  • As the base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin, glycerol, gelatin, and the like can be used.
  • the pharmaceutical composition may further include a carrier, excipient or diluent.
  • Carriers, excipients, or diluents include, for example, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, or mineral oil.
  • the pharmaceutical composition may further include a known active ingredient having a preventive or therapeutic activity for cancer cachexia.
  • the effective dose for the human body of the complex extract of dandelion ginseng and rhubarb of the present invention may vary depending on the patient's age, weight, sex, dosage form, health condition and disease level, and is generally about 0.001 to 100 mg/kg/day and preferably 0.01 to 35 mg/kg/day. Based on an adult patient weighing 70 kg, it is generally 0.07 to 7000 mg/day, preferably 0.7 to 2500 mg/day, and once a day at regular time intervals according to the judgment of a doctor or pharmacist It may be administered in several divided doses.
  • Health functional food and health food composition for preventing or improving cachexia
  • the present invention provides a health functional food composition for preventing or improving cachexia comprising a complex extract of Salviae Miltiorrhizae Radix and rhubarb (Rhei Radix et Rhizoma).
  • the present invention provides a health food composition for preventing or improving cachexia comprising a complex extract of Salviae Miltiorrhizae Radix and rhubarb (Rhei Radix et Rhizoma).
  • the cachexia may be caused by cancer.
  • the health functional food composition or health food composition according to the present invention may improve one or more symptoms selected from the group consisting of decreased appetite, weight loss, increased fatigue, increased inflammation, muscle loss, fat loss, and hematopoietic toxicity, Preferably, it may be to improve one or more symptoms selected from the group consisting of weight loss and fat loss.
  • the health functional food composition or health food composition according to the present invention may simultaneously exhibit an anticancer effect and a cancerous cachexia inhibitory effect.
  • the anticancer effect may be shown through activation of one or more factors selected from the group consisting of Bax and caspase 3.
  • it may be one that exhibits a cancer cell death effect by caspase cascade activation.
  • the complex extract of ginseng and rhubarb showed an effect of improving weight loss and fat loss due to cancer tissue in an animal model of obesity/cancer comorbidity, and Bax and By showing the effect of activating the expression of caspase3 and the effect of inhibiting cancer, the effect of improving the cancer cachexia as well as the anticancer effect was confirmed (see Experimental Examples 1 to 3).
  • health functional food used in the present invention refers to food manufactured and processed in the form of tablets, capsules, pills, liquids, powders and granules, etc. using raw materials or ingredients useful for the human body.
  • 'functionality' refers to obtaining useful effects for health purposes, such as regulating nutrients or physiological effects on the structure and function of the human body.
  • the health functional food of the present invention can be manufactured by a method commonly used in the ordinary technical field, and at the time of the preparation, it can be prepared by adding raw materials and components commonly added in the conventional technical field.
  • the dosage form of the health functional food may also be manufactured without limitation as long as it is a dosage form recognized as a health functional food.
  • the health functional food composition of the present invention can be prepared in various types of dosage forms, and unlike general drugs, it has the advantage of not having side effects that may occur during long-term administration of drugs using food as a raw material, and has excellent portability,
  • the health functional food of the present invention can be ingested as an adjuvant for enhancing the effect of a cancer cachexia therapeutic agent or an anticancer agent.
  • the health functional food composition or health food composition according to the present invention can be added to health functional food or health food such as food, beverage, etc. for the purpose of preventing or improving cancerous cachexia.
  • Examples of foods to which the complex extract of ginseng and rhubarb according to the present invention can be added include drinks, meat, sausage, bread, biscuits, rice cakes, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice creams Dairy products, various soups, beverages, alcoholic beverages and vitamin complexes, dairy products and dairy products including
  • the health functional food and health food composition according to the present invention may be added to food as it is or used together with other food or food ingredients, and may be appropriately used according to a conventional method.
  • the mixing amount of the complex extract of dandelion ginseng and rhubarb according to the present invention may be suitably determined according to the purpose of its use (for prevention or improvement).
  • the amount of the complex extract of ginseng and rhubarb in health food and health functional food may be added in an amount of 0.1 to 90 parts by weight of the total food weight.
  • the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount greater than the above range.
  • the health food and health functional food composition of the present invention is not particularly limited in other ingredients except for containing the complex extract of ginseng and rhubarb according to the present invention as essential ingredients in the indicated ratio, and various flavoring agents or natural Carbohydrates and the like may be contained as additional ingredients.
  • natural carbohydrates include monosaccharides such as glucose, fructose and the like; disaccharides such as maltose, sucrose and the like; and polysaccharides such as conventional sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • natural flavoring agents taumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.
  • the proportion of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 g of the dietary supplement of the present invention.
  • health food and health functional food composition containing the complex extract of ginseng and rhubarb according to the present invention are various nutrients, vitamins, minerals (electrolytes), synthetic flavoring agents and flavoring agents such as natural flavoring agents, coloring agents and thickening agents (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonates used in carbonated drinks, etc.
  • the health food and health functional food composition of the present invention may contain natural fruit juice, fruit juice, and fruit for the production of a vegetable drink.
  • the proportion of these additives is not limited thereto, but is generally selected from 0.1 to about 20 parts by weight per 100 parts by weight of the health food and health functional food composition containing the active substance of the present invention.
  • the present invention provides an anti-cancer adjuvant composition comprising the pharmaceutical composition for preventing or treating cachexia according to the present invention.
  • anticancer adjuvant used in the present invention may be used to increase the anticancer therapeutic effect, suppress or improve the side effects of anticancer agents, and may be administered to a patient in combination with an anticancer agent.
  • the anticancer adjuvant composition of the present invention exhibits an effect of suppressing or improving cachexia symptoms such as muscle loss, weight loss, fat reduction, hematopoiesis, and decreased appetite caused by cancer, thereby increasing the anticancer effect of the anticancer agent. .
  • Existing anticancer agents as defined herein include cisplatin, cyclophosphamide, methotrexate, 5-fluorouracil, doxorubicin, mustine, vicristine ( vincristine), procarbazine, prednisolone, bleomycin, vinblastine, dacarbazine, etoposide, epirubicin, cisplatin ( cisplatin), capecitabine, oxaliplatin, and the like.
  • the anticancer adjuvant composition may further include one or more active ingredients exhibiting the same or similar function in addition to including the complex extract of dandelion ginseng and rhubarb as active ingredients.
  • the anticancer adjuvant can be administered orally or parenterally during clinical administration, and when administered parenterally, intraperitoneal injection, intrarectal injection, subcutaneous injection, intravenous injection, intramuscular injection, intrauterine dural injection, intracerebrovascular injection, or thoracic It can be administered by internal injection, and can be used in the form of general pharmaceutical preparations.
  • the anticancer adjuvant may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers.
  • the daily dose of the anticancer adjuvant is about 0.0001 to 1000 mg/kg, preferably 1 to 100 mg/kg, and it is preferable to divide and administer it once to several times a day, but the patient's weight, age, sex, health condition, The range varies depending on the diet, administration time, administration method, excretion rate, and the severity of the disease.
  • the anticancer adjuvant of the present invention may be administered in various parenteral formulations during actual clinical administration.
  • a diluent or excipient such as a commonly used filler, extender, binder, wetting agent, disintegrant, surfactant, etc.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories.
  • Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.
  • As the base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like can be used.
  • the present invention also provides a method for preventing or treating cachexia, comprising administering to a patient the pharmaceutical composition for preventing or treating cachexia according to the present invention.
  • the treatment method of the present invention comprises administering the pharmaceutical composition to a subject in a therapeutically effective amount.
  • a specific therapeutically effective amount for a particular subject will depend on the type and extent of the response to be achieved, the specific composition, including whether other agents are used, if necessary, the subject's age, weight, general health, sex and diet, time of administration; It is preferable to apply differently depending on various factors including the route of administration and secretion rate of the composition, the duration of treatment, the drug used together with or concurrently with the specific composition, and similar factors well known in the pharmaceutical field. Therefore, it is preferable to determine the effective amount of the composition suitable for the purpose of the present invention in consideration of the foregoing.
  • the patient is applicable to any mammal, and the mammal includes not only humans and primates, but also domestic animals such as cattle, pigs, sheep, horses, dogs and cats.
  • the method for preventing or treating cachexia of the present invention may be a method for simultaneously preventing or treating cachexia and cancer caused by cancer.
  • Herbal medicine complex extract containing dandelion (Salviae miltiorrhizae Radix) and rhubarb (Rhei Radix et Rhizoma) was prepared by hot water extraction by mixing ginseng and rhubarb in a weight ratio of 1:1. Specifically, after trimming and washing ginseng and rhubarb medicinal materials, 250 g of ginseng and 250 g of rhubarb were mixed, put in 1 L of distilled water, and boiled at 100° C. for 2 hours to make 500 ml. The broth was freeze-dried to prepare a powdered ginseng and rhubarb complex extract (Example 1, DD).
  • the yields of rhubarb and dandelion extract were 20.80% and 31.72%, respectively.
  • Each of the extract powders was dissolved in tertiary distilled water, and then filtered through a 22 ⁇ m filter and used in the experiment.
  • the body weight change of the mice was measured during the treatment period for a total of 8 weeks in the same manner as in Example 1.
  • the tumor weight after a total of 8 weeks of treatment and the total weight of the mice minus the cancer tissue weight were compared.
  • the measurement results of each weight are as shown in FIG. 1 .
  • Example 1 when the complex extract (DD) of Example 1 was treated in the animal model of obesity/cancer comorbidity, the tumor weight was significantly (p ⁇ 0.05) reduced compared to the disease control group, and this reduction was shown to have a similar level of efficacy to that of the anticancer drug cisplatin (CIS) (FIG. 1B).
  • the weight (tumor free body weight) excluding the cancer weight when treated with the complex extract (DD) of Example 1 in the animal model of obesity / cancer comorbidity was measured similarly to the disease control group (HFD + B16BL6 injection), When the anticancer drug cisplatin (CIS) was treated, it was significantly (p ⁇ 0.05) reduced compared to the disease control group ( FIG. 1C ).
  • the complex extract (DD) of Example 1 when the complex extract (DD) of Example 1 was treated, the reduction in fat caused by cancer tissue was significantly inhibited compared to the disease control group (HFD+B16BL6 injection), and the control group (HFD) and It was confirmed that almost the same weight could be maintained (FIG. 1E).
  • the anticancer agent cisplatin
  • the complex extract (DD) of Example 1 of the present invention is It was confirmed that it exhibits an excellent inhibitory effect on cancerous cachexia by significantly inhibiting weight loss and fat loss caused by cancer tissue while exhibiting an anticancer effect similar to that of .
  • Example 1 of the present invention In order to measure the effect of the complex extract (DD) of Example 1 of the present invention on the expression of apoptosis factors in the cancer tissue of the animal model, representative of the mitochondrial inner and outer membrane proteins, Bcl-family, Bcl-xl And the change in the expression level of caspase 3 representatively in the caspase cascade, which is the main mechanism of the expression level of Bax and apoptosis, was confirmed using Western blot.
  • DD complex extract
  • Cancer tissue cells of the animal model treated with the complex extract (DD) or cisplatin (CIS) in Experimental Examples 1 and 2 were treated with RIPA buffer [50 mM Tris-HCl (pH 7.5), 0.1% sodium dodecyl sulfate (sodium dodecyl sulphate) , SDS), 0.1% Triton X-100, 1% Nonidet P-40, 0.5% sodium deoxycholate, 150 mM NaCl and 1 mM phenylmethylsulphonyl fluoride] , 8% sodium dodecyl sulfate-polyacrylamide gel (sodium dodecyl sulfatepolyacrylamide gel) was separated by electrophoresis and transferred to a nitrocellulose membrane.
  • RIPA buffer 50 mM Tris-HCl (pH 7.5), 0.1% sodium dodecyl sulfate (sodium dodecyl sulphate) , SDS), 0.1% Triton X
  • the membranes were blocked with TBST (10 mM Tris, 150 mM NaCl and 0.05% Tween20, pH 7.6) with 5% skim milk at room temperature for 1 h, washed with TBST, and then Bax, Bcl-xL, Caspase 3 (Thermo Scientific, Waltham, MA, USA) or actin ( ⁇ -actin, Santa Cruz Biotechnology, Inc.) were incubated overnight at 4°C with primary antibodies. Then, the membrane was reacted with a secondary antibody (Amersham Biosciences, Westborough, MA, USA) to which an appropriate horseradish peroxidase (Jackson Lab.) was attached at room temperature for 2 hours. The target protein band was measured in the LAS Image Gauge program using an enhanced chemiluminescence (ECL) solution (Amersham Bioscience, Piscataway, NJ) according to the manufacturer's instructions, and the results are shown in FIG. indicated.
  • ECL enhanced chemiluminescence
  • the ratio of Bax/Bcl-xL was increased in the complex extract (DD) treated group compared to the disease control group, and in particular, it was found that the ratio of cleaved/pro caspase 3 was significantly increased, so caspase cascade It was confirmed that there is a cancer inhibitory effect by activation.

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Abstract

La présente invention concerne une composition pour la prévention, l'amélioration ou le traitement de la cachexie, comprenant un extrait complexe de Salviae miltiorrhizae radix et de Rhei radix et rhizoma, l'extrait complexe éliminant la perte de poids et la perte de graisse provoquées par un cancer, et induisant la mort des cellules cancéreuses, et peut, par conséquent, être efficacement utilisée en tant que composition pour la prévention, l'amélioration ou le traitement de la cachexie cancéreuse, la composition permettant simultanément un traitement anticancéreux sans les effets secondaires de la cachexie et l'amélioration de la cachexie.
PCT/KR2020/015608 2020-11-09 2020-11-09 Composition pour la prévention ou le traitement de la cachexie, contenant un extrait complexe de salviae miltiorrhizae radix et de rhei radix et rhizoma WO2022097794A1 (fr)

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PCT/KR2020/015608 WO2022097794A1 (fr) 2020-11-09 2020-11-09 Composition pour la prévention ou le traitement de la cachexie, contenant un extrait complexe de salviae miltiorrhizae radix et de rhei radix et rhizoma
JP2023527759A JP2023548411A (ja) 2020-11-09 2020-11-09 タンジンおよびダイオウの複合抽出物を含む悪液質予防または治療用組成物

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PCT/KR2020/015608 WO2022097794A1 (fr) 2020-11-09 2020-11-09 Composition pour la prévention ou le traitement de la cachexie, contenant un extrait complexe de salviae miltiorrhizae radix et de rhei radix et rhizoma

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JP2009004390A (ja) * 2008-10-03 2009-01-08 Sony Corp 蛍光ランプ及び表示装置
KR20120040026A (ko) * 2010-10-18 2012-04-26 동국대학교 경주캠퍼스 산학협력단 단삼을 포함하는 신부전 예방 및 치료용 약제학적 조성물
JP5300195B2 (ja) * 2003-09-08 2013-09-25 ジェニオウス バイオメド インターナショナル インコーポレイテッド 癌治療のための植物性薬品抽出物の組成物
KR102146463B1 (ko) * 2018-10-18 2020-08-21 한명석 대황 추출물 또는 이의 분획물을 유효성분으로 함유하는 근육질 개선용 조성물

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JP2009004390A (ja) * 2008-10-03 2009-01-08 Sony Corp 蛍光ランプ及び表示装置
KR20120040026A (ko) * 2010-10-18 2012-04-26 동국대학교 경주캠퍼스 산학협력단 단삼을 포함하는 신부전 예방 및 치료용 약제학적 조성물
KR102146463B1 (ko) * 2018-10-18 2020-08-21 한명석 대황 추출물 또는 이의 분획물을 유효성분으로 함유하는 근육질 개선용 조성물

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