WO2022097794A1 - Composition for preventing or treating cachexia, containing complex extract of salviae miltiorrhizae radix and rhei radix et rhizoma - Google Patents

Composition for preventing or treating cachexia, containing complex extract of salviae miltiorrhizae radix and rhei radix et rhizoma Download PDF

Info

Publication number
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
Authority
WO
WIPO (PCT)
Prior art keywords
cancer
cachexia
composition
preventing
complex extract
Prior art date
Application number
PCT/KR2020/015608
Other languages
French (fr)
Korean (ko)
Inventor
엄재영
안광석
이석근
양웅모
정윤우
박진봉
Original Assignee
경희대학교 산학협력단
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 경희대학교 산학협력단 filed Critical 경희대학교 산학협력단
Priority to PCT/KR2020/015608 priority Critical patent/WO2022097794A1/en
Priority to JP2023527759A priority patent/JP2023548411A/en
Publication of WO2022097794A1 publication Critical patent/WO2022097794A1/en

Links

Images

Classifications

    • 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.

Abstract

The present invention relates to a composition for preventing, ameliorating or treating cachexia, comprising a complex extract of Salviae miltiorrhizae radix and Rhei radix et rhizoma, wherein the complex extract suppresses weight loss and fat loss caused by cancer, and induces cancer cell death, and thus, can be useful as a composition for preventing, ameliorating, or treating cancer cachexia, the composition enabling anti-cancer treatment without cachexia side effects and cachexia amelioration simultaneously.

Description

단삼 및 대황의 복합추출물을 포함하는 악액질 예방 또는 치료용 조성물Composition for the prevention or treatment of cachexia comprising a complex extract of ginseng and rhubarb
본 발명은 한약복합추출물을 포함하는 악액질 예방, 개선 또는 치료용 조성물에 관한 것으로, 더욱 상세하게는 단삼(Salviae Miltiorrhizae Radix) 및 대황(Rhei Radix et Rhizoma)의 복합추출물을 포함하는 암성 악액질 예방, 개선 또는 치료용 약학적 조성물, 건강기능식품 조성물 및 항암 보조제 조성물에 관한 것이다.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.
악액질(cachexia)은 암, 심부전증, 만성 폐쇄성 폐 질환, 만성 신장 질환, 에이즈 등의 다양한 질병에 의해 지속적인 근육 손실을 일으키는 복잡한 증후군을 가리킨다. 이 중 암성 악액질(cancer cachexia)은 악성 종양을 수반하는 복합 대사 증후군으로서, 암이 발생하고 6개월 내에 근육과 지방의 손실에 의해 체중이 5% 이상 감소하는 것으로 정의된다. 악액질은 다양한 의학적 상태에서 일어날 수 있으나 암성 악액질은 말기 암과 밀접한 관계를 가지고 있다. 전체 암 환자의 약 50%, 특히 암 말기 환자의 약 80%가 암성 악액질의 영향을 받으며 근육 및/또는 지방의 손실로 인한 삶의 저하 및 사망률 증가로 인해 고통 받고 있다. 암성 악액질은 근육량 및/또는 지방 조직의 현저한 손실을 통한 체중 감소가 특징이며, 식욕 억제를 통한 근육 및 지방 손실과는 다른 특징을 지니고 있다.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. Among them, 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.
암성악액질의 치료제에는 NSAIDs (non-steroidal anti-inflammatory drugs), β2-adrenergic agonists, corticosteroid, ghrelin 등이 있으며, 현재까지 시판되고 있는 암성 악액질 치료에 가장 많이 사용되는 약물은 COX-2 억제제와 TNF-α 억제제가 있다.Treatments for cancer cachexia include NSAIDs (non-steroidal anti-inflammatory drugs), β2-adrenergic agonists, corticosteroids, and ghrelin. There are α inhibitors.
COX-2 억제제는 암 조직에서 다량 발생되는 염증 물질인 프로스타글란딘(prostaglandins)의 생성에 관여하는 COX-2를 억제하여 골격근의 손실을 감소시키는 약물이다. COX-2 억제제로서 시중에는 셀레콕시브(celecoxib)가 판매되고 있다. 그러나 셀레콕시브(celecoxib)는 빈혈, 위궤양, 알레르기, 심장 마비 및 뇌졸중 등의 부작용이 보고되어 있다.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. 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.
TNF-α 억제제는 암성 악액질 환자의 혈정에서 많이 발현되는 TNF-α 의 발현을 감소시켜 암세포를 사멸시키는 약물이다. TNF-α 억제제로서 시중에는 탈리도마이드(Thalidomide)가 판매되고 있다. 그러나 이들 약물은 암성 악액질 치료제로서의 효과가 적으며, 우울증, 심부전, 호흡 곤란, 구토, 발진, 고혈압 및 임신 시 기형아를 낳게 되는 부작용이 있다.A TNF-α inhibitor is a drug that kills cancer cells by reducing the expression of TNF-α, which is often expressed in the bloodstream of patients with cancer cachexia. Thalidomide is commercially available as a TNF-α inhibitor. However, 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.
이와 같이 현재까지 개발 중이거나 시판되고 있는 약물은 대부분 부작용이 많이 나타나며, 치료 효과에 대한 근거가 부족하다. 따라서 새로운 기전의 암성 악액질 치료제 개발이 절실한 상황이다.As such, most of the drugs being developed or marketed up to now have many side effects and lack of evidence for their therapeutic effect. Therefore, there is an urgent need to develop a treatment for cancer cachexia with a new mechanism.
한편, 단삼(Salviae Miltiorrhizae Radix)은 꿀풀과(Lamiaceae)에 속한 단삼(Salvia miltiorrhiza Bunge)의 뿌리를 기원으로 하는 한약재로서, 심혈관계 및 다양한 혈관질환에 대한 작용, 간, 폐 및 신장의 손상억제, 골다공증에 대한 활성, 중추신경계 작용, 항염증, 항산화, 항암작용에 대한 활성을 나타낸 바 있다.On the other hand, 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.
대황(Rhei Radix et Rhizoma)은 마디풀과(Polygonaceae)에 속한 다년생 초본류인 장엽대황(Rheum palmatum Linne), 탕구트대황(Rheum tanguticum Maximowicz ex Balf.) 또는 약용대황(Rheum officinale Baillon)의 뿌리 및 뿌리줄기로서 주피를 제거한 것으로, 임상적으로 소화불량, 변비, 급성염증, 전염병, 기생충병, 출혈, 혈소판 감소증, 화상 및 피부병의 치료에 응용된다.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.
본 발명자들은 천연물인 단삼 및 대황의 복합추출물이 비만/암 동반질환 동물모델에서 암에 의한 체중감소 및 지방 손실을 억제하고, 암 세포사멸을 유도하여, 유의성 있는 항암 및 암성 악액질 개선 효과가 있음을 확인하여, 본 발명을 완성하였다.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.
본 발명의 목적은, 악액질(cachexia) 예방 또는 치료용 약학적 조성물을 제공하는 것이다.It is an object of the present invention to provide a pharmaceutical composition for preventing or treating cachexia.
본 발명의 다른 목적은, 악액질 예방 또는 개선용 건강기능식품 조성물 및 건강식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a health functional food composition and health food composition for preventing or improving cachexia.
본 발명의 또 다른 목적은, 상기 약학적 조성물을 포함하는 항암 보조제 조성물을 제공하는 것이다.Another object of the present invention is to provide an anticancer adjuvant composition comprising the pharmaceutical composition.
본 발명의 또 다른 목적은, 악액질 예방 또는 치료 방법을 제공하는 것이다.Another object of the present invention is to provide a method for preventing or treating cachexia.
상기 목적을 달성하기 위하여,In order to achieve the above object,
본 발명은, 단삼(Salviae Miltiorrhizae Radix) 및 대황(Rhei Radix et Rhizoma)의 복합추출물을 포함하는 악액질(cachexia) 예방 또는 치료용 약학적 조성물을 제공한다.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).
본 발명의 일실시예에 있어서, 상기 악액질은 암에 의해 유발되는 것일 수 있다.In one embodiment of the present invention, the cachexia may be caused by cancer.
또한, 본 발명은, 단삼 및 대황의 복합추출물을 포함하는 악액질 예방 또는 개선용 건강기능식품 조성물 및 건강식품 조성물을 제공한다.In addition, 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.
나아가, 본 발명은, 상기 악액질 예방 또는 치료용 약학적 조성물을 포함하는 항암 보조제 조성물을 제공한다.Furthermore, the present invention provides an anti-cancer adjuvant composition comprising the pharmaceutical composition for preventing or treating cachexia.
더 나아가, 본 발명은 상기 악액질 예방 또는 치료용 약학적 조성물을 환자에게 투여하는 것을 포함하는 악액질 예방 또는 치료 방법을 제공한다.Furthermore, the present invention provides a method for preventing or treating cachexia comprising administering to a patient the pharmaceutical composition for preventing or treating cachexia.
본 발명의 단삼 및 대황의 복합추출물은 비만/암 동반질환 동물모델에서 암에 의한 체중 감소 및 지방 손실을 억제하고, caspase cascade 활성화를 통해 암 세포사멸을 유도함으로써, 유의성 있는 항암 및 암성 악액질 개선 효과를 나타내므로, 악액질 부작용 없이 항암 치료 및 악액질 개선이 동시에 가능한 암성 악액질 예방, 개선 또는 치료용 조성물로 유용할 수 있다.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.
도 1은 본 발명의 단삼 및 대황의 복합추출물 처리에 따른 비만/암 동반질환 동물모델의 체중 변화(body weight change), 암 조직의 무게(tumor weight), 전체 쥐의 체중에서 암 조직의 무게를 제외한 체중(cancer free body weight), 피하지방(inguinal white adipose tissue, iWAT) 및 복부내장지방(epididymal white adipose tissue, eWAT)의 무게 변화를 측정한 결과를 나타낸 것이다.1 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 The results of measuring changes in weight of excluding body weight (cancer free body weight), subcutaneous fat (inguinal white adipose tissue, iWAT), and visceral fat (epididymal white adipose tissue, eWAT) are shown.
도 2는 단삼 및 대황의 복합추출물의 암 세포사멸 관련 인자(Bcl-xl, Bax, cleaved-caspase 3 및 caspase 3) 발현에 대한 효과를 나타낸 것이다.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.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
악액질 예방 또는 치료용 약학적 조성물Pharmaceutical composition for preventing or treating cachexia
본 발명은 단삼(Salviae Miltiorrhizae Radix) 및 대황(Rhei Radix et Rhizoma)의 복합추출물을 포함하는 악액질(cachexia) 예방 또는 치료용 약학적 조성물을 제공한다.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).
본 명세서에 사용된 용어, '악액질(cachexia)'은 암, 결핵, 당뇨병, 후천성면역결핍증(Acquired immunodeficiency syndrome, AIDS) 등의 말기에서 볼 수 있는 고도의 전신쇠약증세를 말하며, 위암이나 식도암, 췌장암, 대장암 등 소화기암 환자와 폐암 환자에서 자주 나타난다. 식욕 감소, 근육 및 지방 감소에 따른 체중 및 체력의 감소, 빈혈, 무기력, 소화 불량 등의 증상 등을 나타내며, 특히 정상적으로 음식을 섭취하더라도 체중이 감소하는 상태를 나타낸다. 악액질이 발생하면 항암 화학요법이나 방사선 치료에 대해 낮은 반응을 보이므로 환자의 삶의 질이 저하되고, 기대 여명의 단축을 초래하며, 전체 암환자의 10 내지 20%에서 체중 감소로 인한 사망을 유발한다.As used herein, 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.
본 발명에 따른 약학적 조성물에 있어서, 상기 악액질은 암에 의해 유발되는 것일 수 있다. 본 발명의 일실시예에서는, 상기 암에 의해 유발되는 악액질을 '암성 악액질(cancer cachexia)'이라 표현하였다.In the pharmaceutical composition according to the present invention, the cachexia may be caused by cancer. In one embodiment of the present invention, cachexia induced by the cancer is expressed as 'cancer cachexia'.
본원에서 정의되는 암은 흑색종, 백혈병, 림프종, 골수종, 골수이형성증후군, 유방암, 두경부암, 식도암, 위암, 대장암(=결장암), 직장암, 항문암, 간세포간암, 담관암, 담낭암, 췌장암, 폐암(비소세포성 폐암, 소세포성 폐암), 흉선암, 신장암, 방광암, 전립선암, 고환암, 난소암, 자궁경부암, 육종, 위장관 기질성 종양(GIST, 기스트), 원발부위불명암, 중피종, 신경내분비 종양, 피부암, 혈액암 등을 포함하는 것일 수 있다.Cancer as defined herein is melanoma, leukemia, lymphoma, myeloma, myelodysplastic syndrome, breast cancer, head and neck cancer, esophageal cancer, stomach cancer, colorectal cancer (= colon cancer), rectal cancer, anal cancer, hepatocellular liver cancer, bile duct cancer, gallbladder cancer, pancreatic cancer, lung cancer (Non-small cell lung cancer, small cell lung cancer), thymus cancer, kidney cancer, bladder cancer, prostate cancer, testicular cancer, ovarian cancer, cervical cancer, sarcoma, gastrointestinal stromal tumor (GIST, GIST), cancer of unknown primary site, mesothelioma, It may include neuroendocrine tumors, skin cancers, blood cancers, and the like.
본 발명에 따른 상기 약학적 조성물은 식욕 감소, 체중 감소, 피로도 증가, 염증 증가, 근육 손실, 지방 손실 및 조혈 독성으로 이루어진 군에서 선택되는 1종 이상의 증상을 개선하는 것일 수 있고, 바람직하게는 체중 감소 및 지방 손실로 이루어진 군에서 선택되는 1종 이상의 증상을 개선하는 것일 수 있다.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.
본 발명에 따른 상기 약학적 조성물은 항암 효과 및 암성 악액질 억제 효과를 동시에 나타내는 것일 수 있다.The pharmaceutical composition according to the present invention may simultaneously exhibit an anticancer effect and a cancerous cachexia inhibitory effect.
상기 항암 효과는 Bax 및 caspase 3로 이루어진 군으로부터 선택되는 1종 이상의 인자의 활성화를 통해 나타나는 것일 수 있다. 바람직하게는 caspase cascade 활성화에 의해 암 세포사멸 효과를 나타내는 것일 수 있다.The anticancer effect may be shown through activation of one or more factors selected from the group consisting of Bax and caspase 3. Preferably, it may be one that exhibits a cancer cell death effect by caspase cascade activation.
본 발명의 일실시예에 따르면, 단삼 및 대황의 복합추출물이 비만/암 동반질환 동물모델에서 암 조직에 의한 체중 감소 및 지방 손실을 개선시키는 효과를 보였고, 암 세포사멸의 인자로서 작용하는 Bax 및 caspase3의 발현을 활성화하는 효과 및 암을 억제하는 효과를 나타냄으로써, 항암 효과와 동시에 암성 악액질을 개선시키는 효과를 확인하였다(실험예 1 내지 3 참조).According to an embodiment of the present invention, 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).
상기와 같은 효과는, 본 발명의 단삼 및 대황의 복합추출물이 각 단독 추출물 대비 효과가 현저히 증가되는 것일 수 있다.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.
본 발명에서, 상기 단삼 및 대황의 복합추출물은 단삼 및 대황을 혼합한 혼합물을 추출한 것일 수 있고, 단삼 및 대황 각각을 추출한 추출물들을 혼합한 것일 수 있으나, 이에 제한되지는 않는다.In the present invention, 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.
상기 "추출물(extract)"은 추출 대상을 적절한 침출액으로 짜내고 침출액을 증발시켜 농축한 제제를 의미하는 것으로, 이에 제한되지는 않으나, 추출처리에 의해 얻어지는 추출액, 추출액의 희석액 또는 농축액, 추출액을 건조하여 얻어지는 건조물, 이들의 조정제물 또는 정제물일 수 있다. 상기 추출방법으로는, 이에 제한되지는 않으나, 바람직하게 열탕 추출, 열수 추출, 냉침 추출, 환류 냉각 추출 또는 초음파 추출 등의 방법을 사용할 수 있다.The "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.
예를 들어, 상기 복합추출물은 단삼 및 대황을 혼합하는 단계; 및 상기 혼합물을 물, C1 내지 C4의 알코올, 에틸아세테이트, 또는 이들의 혼합물로 침지하여 추출물을 수득하는 단계;를 포함하는 방법으로 제조되는 것일 수 있으나, 이에 제한되지는 않는다. 이때, 상기 C1 내지 C4의 알코올은 에탄올, 메탄올, 부탄올, 또는 이들의 조합일 수 있다. 상기 추출용매를 단삼 및 대황 혼합물 중량의 1 내지 10배 부피의 양으로 첨가하여 추출하는 것일 수 있다. 추출온도는 30 내지 120℃인 것일 수 있으나, 이에 한정되는 것은 아니다. 또한, 추출시간은 2 내지 48시간인 것일 수 있으나, 이에 한정되는 것은 아니다. For example, 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. In this case, 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 ℃, but is not limited thereto. In addition, the extraction time may be 2 to 48 hours, but is not limited thereto.
상기 단삼 및 대황은 0.1:10~10:0.1의 중량비로 혼합하는 것일 수 있고, 바람직하게는 0.5:5~5:0.5의 중량비로 혼합하는 것일 수 있고, 더 바람직하게는 1:3~3:1의 중량비로 혼합하는 것일 수 있고, 1:2~2:1의 중량비로 혼합하는 것이 가장 바람직한 것일 수 있다.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.
상기 추출방법은 추출물을 물, C1 내지 C4 알코올, 또는 이들의 조합으로 분획하는 단계를 더 포함할 수 있다. 바람직하게는, 물, 에탄올, 메탄올, 부탄올, 에틸아세테이트, 헥산 또는 이들의 조합으로 분획될 수 있다. 상기 추출방법은 추출물을 농축, 원심분리, 여과, 흡착, 또는 크로마토그래피를 수행하는 단계를 더 포함할 수 있다.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.
본 발명에 따른 상기 약학적 조성물은 경구 투여용, 근육내 투여용, 정맥내 투여용, 복강내 투여용, 피하 투여용, 피내 투여용, 또는 국소 투여용으로 제제화되는 것일 수 있다.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.
본 발명의 단삼 및 대황의 복합추출물은 임상 투여시에 경구 및 비경구의 여러 가지 제형으로 투여될 수 있으며, 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 제조된다.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.
경구투여를 위한 고형 제제에는 정제, 환자, 산제, 과립제, 캡슐제, 트로키제 등이 포함되며, 이러한 고형 제제는 하나 이상의 본 발명의 단삼 및 대황의 복합추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 탄산칼슘, 수크로스(sucrose), 락토오스(lactose) 또는 젤라틴 등을 섞어 조제된다. 또한, 단순한 부형제 외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구 투여를 위한 액상 제제로는 현탁제, 내용액제, 유제 또는 시럽제 등이 해당되는데, 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다.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
비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁용제, 유제, 동결건조제제, 좌제 등이 포함된다. 비수성용제, 현탁용제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세롤, 젤라틴 등이 사용될 수 있다.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. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin, glycerol, gelatin, and the like can be used.
상기 약학적 조성물은 담체, 부형제 또는 희석제를 더 포함할 수 있다. 담체, 부형제, 또는 희석제는 예를 들어, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알기네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오스, 메틸 셀룰로스, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트, 또는 광물유를 포함할 수 있다.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.
또한, 상기 약학적 조성물은 암성 악액질 예방 또는 치료 활성을 갖는 공지의 유효성분을 더 포함할 수 있다.In addition, the pharmaceutical composition may further include a known active ingredient having a preventive or therapeutic activity for cancer cachexia.
본 발명의 단삼 및 대황의 복합추출물의 인체에 대한 효과적인 투여량은 환자의 나이, 몸무게, 성별, 투여형태, 건강상태 및 질환 정도에 따라 달라질 수 있으며, 일반적으로 약 0.001~100 mg/kg/일이며, 바람직하게는 0.01~35 mg/kg/일이다. 몸무게가 70 ㎏인 성인 환자를 기준으로 할 때, 일반적으로 0.07~7000 mg/일이며, 바람직하게는 0.7~2500 ㎎/일이며, 의사 또는 약사의 판단에 따라 일정시간 간격으로 1일 1회 내지 수회로 분할 투여할 수도 있다.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.
악액질 예방 또는 개선용 건강기능식품 및 건강식품 조성물Health functional food and health food composition for preventing or improving cachexia
또한, 본 발명은 단삼(Salviae Miltiorrhizae Radix) 및 대황(Rhei Radix et Rhizoma)의 복합추출물을 포함하는 악액질(cachexia) 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, 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).
나아가, 본 발명은 단삼(Salviae Miltiorrhizae Radix) 및 대황(Rhei Radix et Rhizoma)의 복합추출물을 포함하는 악액질(cachexia) 예방 또는 개선용 건강식품 조성물을 제공한다.Furthermore, 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).
본 발명에 따른 건강기능식품 조성물 또는 건강식품 조성물에 있어서, 상기 악액질은 암에 의해 유발되는 것일 수 있다.In the health functional food composition or health food composition according to the present invention, the cachexia may be caused by cancer.
본 발명에 따른 건강기능식품 조성물 또는 건강식품 조성물은 식욕 감소, 체중 감소, 피로도 증가, 염증 증가, 근육 손실, 지방 손실 및 조혈 독성으로 이루어진 군에서 선택되는 1종 이상의 증상을 개선하는 것일 수 있고, 바람직하게는 체중 감소 및 지방 손실로 이루어진 군에서 선택되는 1종 이상의 증상을 개선하는 것일 수 있다.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.
본 발명에 따른 건강기능식품 조성물 또는 건강식품 조성물은 항암 효과 및 암성 악액질 억제 효과를 동시에 나타내는 것일 수 있다.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.
상기 항암 효과는 Bax 및 caspase 3로 이루어진 군으로부터 선택되는 1종 이상의 인자의 활성화를 통해 나타나는 것일 수 있다. 바람직하게는 caspase cascade 활성화에 의해 암 세포사멸 효과를 나타내는 것일 수 있다.The anticancer effect may be shown through activation of one or more factors selected from the group consisting of Bax and caspase 3. Preferably, it may be one that exhibits a cancer cell death effect by caspase cascade activation.
본 발명의 일실시예에 따르면, 단삼 및 대황의 복합추출물이 비만/암 동반질환 동물모델에서 암 조직에 의한 체중 감소 및 지방 손실을 개선시키는 효과를 보였고, 암 세포사멸의 인자로서 작용하는 Bax 및 caspase3의 발현을 활성화하는 효과 및 암을 억제하는 효과를 나타냄으로써, 항암 효과와 동시에 암성 악액질을 개선시키는 효과를 확인하였다(실험예 1 내지 3 참조).According to an embodiment of the present invention, 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).
본 발명에서 사용되는 용어 "건강기능식품"이란 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 정제, 캡슐제, 환제, 액제, 분말 및 과립 등의 형태로 제조 및 가공한 식품을 말한다. 여기서 '기능성'이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건용도에 유용한 효과를 얻는 것을 의미한다. 본 발명의 건강기능식품은 통상의 기술분야에서 통상적으로 사용되는 방법에 의하여 제조가능하며, 상기 제조시에는 통상의 기술분야에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 또한, 상기 건강기능식품의 제형 또한 건강기능식품으로 인정되는 제형이면 제한없이 제조될 수 있다. 본 발명의 건강기능식품 조성물은 다양한 형태의 제형으로 제조될 수 있으며, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고, 휴대성이 뛰어나, 본 발명의 건강기능식품은 암성 악액질 치료제 또는 항암제의 효과를 증진시키기 위한 보조제로 섭취가 가능하다.The term "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. Here, '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. In addition, 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.
본 발명에 따른 상기 건강기능식품 조성물 또는 건강식품 조성물은 암성 악액질을 예방 또는 개선시키기 위한 목적으로 상기 단삼 및 대황의 복합추출물을 식품, 음료 등의 건강기능식품 또는 건강식품에 첨가할 수 있다.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.
상기 식품의 종류에는 특별한 제한은 없다. 본 발명에 따른 단삼 및 대황의 복합추출물을 첨가할 수 있는 식품의 예로는 드링크제, 육류, 소시지, 빵, 비스킷, 떡, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 알코올 음료 및 비타민 복합제, 유제품 및 유가공 제품 등이 있으며, 통상적인 의미에서의 건강식품 및 건강기능식품을 모두 포함한다.There is no particular limitation on the type of the food. 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
본 발명에 따른 상기 건강기능식품 및 건강식품 조성물은 식품에 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 본 발명에 따른 상기 단삼 및 대황의 복합추출물의 혼합량은 그의 사용 목적(예방 또는 개선용)에 따라 적합하게 결정될 수 있다. 일반적으로, 건강식품 및 건강기능식품 중의 상기 단삼 및 대황의 복합추출물의 양은 전체 식품 중량의 0.1 내지 90 중량부로 가할 수 있다. 그러나 건강 유지를 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.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). In general, 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. However, in the case of long-term intake for health maintenance or health control, 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.
본 발명의 건강식품 및 건강기능식품 조성물은 지시된 비율로 필수 성분으로서 본 발명에 따른 단삼 및 대황의 복합추출물을 함유하는 외에는 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트라이톨 등의 당알코올이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 건강기능성 식품 조성물 100 g당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다.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. Examples of the above-mentioned 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. As flavoring agents other than those described above, 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.
상기 외에 본 발명에 따른 단삼 및 대황의 복합추출물을 함유하는 건강식품 및 건강기능식품 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 건강식품 및 건강기능식품 조성물은 천연 과일쥬스 및 과일쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다.In addition to the above, 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. . In addition, 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.
이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 이에 제한되지는 않으나, 본 발명의 유효물질을 함유하는 건강식품 및 건강기능식품 조성물 100 중량부 당 0.1 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.These components may be used independently or in combination. 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.
항암 보조제 조성물Anti-cancer adjuvant composition
또한, 본 발명은 상기 본 발명에 따른 악액질(cachexia) 예방 또는 치료용 약학적 조성물을 포함하는 항암 보조제 조성물을 제공한다.In addition, the present invention provides an anti-cancer adjuvant composition comprising the pharmaceutical composition for preventing or treating cachexia according to the present invention.
본 발명에서 사용되는 용어 "항암보조제"는 항암 치료 효과를 증대시키고, 항암제의 부작용을 억제하거나 개선시키기 위하여 사용될 수 있으며, 항암제와 병용하여 환자에게 투여될 수 있다.The term "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.
본 발명의 상기 항암 보조제 조성물은, 암에 의해 유발되는 근손실, 체중 감소, 지방 감소, 조혈 도성, 식욕 감소 등의 악액질 증상을 억제하거나 개선시키는 효과를 나타내어 항암제의 항암효과를 증대시키는 것일 수 있다.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. .
본원에서 정의되는 기존 항암제는 시스플라틴(cisplatin), 시클로포스파미드(Cyclophosphamide), 메토트랙세이트 (methotrexate), 5-플루오로우라실(fluorouracil), 독소루비신(Doxorubicin), 무스틴(Mustine), 비크리스틴(vincristine), 프로카바진(procarbazine), 프레드니솔론(prednisolone), 블레오마이신(bleomycin), 빈블라스틴(vinblastine), 다카르바진(dacarbazine), 에토포시드 (etoposide), 에피루비신(Epirubicin), 시스플라틴(cisplatin), 카페시타빈(capecitabine), 옥살리플라틴(oxaliplatin) 등을 포함하는 것일 수 있다.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.
상기 항암 보조제 조성물은 유효성분으로 단삼 및 대황의 복합추출물을 포함하는 이외에 동일 또는 유사한 기능을 나타내는 유효성분을 추가로 1종 이상 포함할 수 있다. 상기 항암 보조제는 임상 투여 시에 경구 또는 비경구로 투여가 가능하며, 비경구 투여 시 복강 내 주사, 직장 내 주사, 피하주사, 정맥주사, 근육 내 주사, 자궁 내 경막주사, 뇌혈관 내 주사 또는 흉부 내 주사에 의해 투여될 수 있고, 일반적인 의약품 제제의 형태로 사용될 수 있다.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.
상기 항암 보조제는 단독으로, 또는 수술, 방사선 치료, 호르몬 치료, 화학 치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다. 상기 항암 보조제의 일일 투여량은 약 0.0001 내지 1000 ㎎/㎏이고, 바람직하게는 1 내지 100 ㎎/㎏이며, 하루 1회 내지 수회 나누어 투여하는 것이 바람직하나 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여 방법, 배설률 및 질환의 중증도 등에 따라 그 범위가 다양하다. 본 발명의 항암 보조제는 실제 임상 투여 시에 비경구의 여러 가지 제형으로 투여될 수 있는데, 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성용제, 현탁용제로는 프로필렌글리콜(Propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.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. When formulated, a diluent or excipient such as a commonly used filler, extender, binder, wetting agent, disintegrant, surfactant, etc. is prepared 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.
또한, 본 발명은 상기 본 발명에 따른 악액질(cachexia) 예방 또는 치료용 약학적 조성물을 환자에게 투여하는 것을 포함하는 악액질(cachexia) 예방 또는 치료 방법을 제공한다.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.
본 발명의 치료 방법은 상기 약학적 조성물을 치료적 유효량으로 개체에 투여하는 것을 포함한다. 특정 개체에 대한 구체적인 치료적 유효량은 달성하고자 하는 반응의 종류와 정도, 경우에 따라 다른 제제가 사용되는지의 여부를 비롯한 구체적 조성물, 개체의 연령, 체중, 일반건강 상태, 성별 및 식이, 투여 시간, 투여 경로 및 조성물의 분비율, 치료기간, 구체적 조성물과 함께 사용되거나 동시 사용되는 약물을 비롯한 다양한 인자와 의약 분야에 잘 알려진 유사 인자에 따라 다르게 적용하는 것이 바람직하다. 따라서 본 발명의 목적에 적합한 조성물의 유효량은 전술한 사항을 고려하여 결정하는 것이 바람직하다.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.
상기 환자는 임의의 포유동물에 적용가능하며, 상기 포유동물은 인간 및 영장류뿐만 아니라, 소, 돼지, 양, 말, 개 및 고양이 등의 가축을 포함한다.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.
본 발명의 상기 악액질 예방 또는 치료 방법은, 암에 의해 유발되는 악액질 및 암을 동시에 예방 또는 치료하는 방법인 것일 수 있다.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.
이하, 본 발명을 하기의 실시예에 의하여 더욱 상세하게 설명한다. 단, 하기의 실시예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기의 실시예에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following examples.
<실시예 1> 단삼 및 대황의 복합추출물의 제조<Example 1> Preparation of complex extract of ginseng and rhubarb
단삼(Salviae miltiorrhizae Radix) 및 대황(Rhei Radix et Rhizoma)을 포함하는 한약 복합추출물은 단삼 및 대황을 1:1의 중량비로 혼합하여 열수추출하여 제조하였다. 구체적으로, 단삼 및 대황 약재를 손질하여 세척한 후 단삼 250 g과 대황 250 g을 혼합하여, 증류수 1L에 넣고, 100℃에서 2시간 동안 전탕하여 500 ml이 되도록 하였다. 전탕액은 동결 건조하여 분말 형태의 단삼 및 대황 복합추출물(실시예 1, DD)을 제조하였다. 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).
또한, 단삼 500g 및 대황 500g 각각을 상기와 동일한 방법을 이용하여, 단삼 단일 추출물 및 대황 단일 추출물을 제조하였다.In addition, using the same method as above for 500 g of dandelion ginseng and 500 g of rhubarb, respectively, a single extract of dandelion and a single extract of rhubarb were prepared.
이때, 대황 및 단삼 추출물 각각의 수율은 20.80% 및 31.72%이었다. 상기 추출물 분말은 각각 3차 증류수에 녹인 후, 22 μm의 필터로 여과하여 실험에 사용하였다.At this time, 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 μm filter and used in the experiment.
<실험예 1> 동물 모델의 준비<Experimental Example 1> Preparation of animal models
본 발명의 추출물의 암성 악액질에 대한 효과를 확인하기 위해, 비만/암 동반 질환 동물모델을 제조하였다.In order to confirm the effect of the extract of the present invention on cancer cachexia, an animal model of obesity/cancer comorbidity was prepared.
구체적으로, 7주령의 C57bl/6j 마우스에 5주 동안 고지방식이를 섭취시킨 후 5주차에 마우스 왼쪽 허벅지에 C57bl/6j 유래 흑색종세포인 B16BL6 세포를 피하주사하여 암(흑색종) 및 비만을 유발하였다. 이 후 추가적으로 3주 동안 모든 그룹에 고지방식이를 먹이면서, 실시예 1의 단삼 및 대황 복합추출물(DD; 경구투여, 주3회) 또는 흑색종 치료에 많이 사용되는 항암제인 시스플라틴(cisplatin, CIS; 복강투여, 주1회)을 투여하였다. 대조군(high fat diet, HFD) 및 질병대조군(HFD+B16BL6 injection)에는 각각 비만 또는 비만/암 유발 후 3주 동안 아무것도 주입하지 않고 고지방식이만 섭취시켰다.Specifically, 7-week-old C57bl/6j mice were fed a high-fat diet for 5 weeks, and then at the 5th week, C57bl/6j-derived melanoma cells, B16BL6 cells, were subcutaneously injected into the left thigh of the mouse to prevent cancer (melanoma) and obesity. induced. After that, while feeding all groups a high-fat diet for an additional 3 weeks, the complex extract of dandelion and rhubarb of Example 1 (DD; oral administration, 3 times a week) or cisplatin (cisplatin, CIS), an anticancer agent widely used in the treatment of melanoma ; intraperitoneal administration, once a week) was administered. Control group (high fat diet, HFD) and disease control group (HFD+B16BL6 injection) were ingested only a high fat diet without injecting anything for 3 weeks after induction of obesity or obesity/cancer, respectively.
<실험예 2> 복합추출물의 암성 악액질에 의한 체중 감소 개선 효과<Experimental Example 2> Weight loss improvement effect by cancer cachexia of the complex extract
암성 악액질의 유발 및 복합추출물의 개선 효과를 확인하기 위해 상기 실시예 1과 같은 방법으로 총 8주간의 처치기간 동안 마우스들의 체중 변화(body weight change)를 측정하였다. 또한 암 조직에 따른 체중의 차이를 보정하기 위해 총 8주간의 처치 후 암 조직의 무게(tumor weight) 및 전체 쥐의 체중에서 암 조직의 무게를 제외한 체중(cancer free body weight)을 비교하였으며, 또한 백색지방조직인 피하지방(inguinal white adipose tissue, iWAT) 및 복부내장지방(epididymal white adipose tissue, eWAT)의 무게 변화를 측정하였다. 각 무게의 측정 결과는 도 1에 나타난 바와 같다.In order to confirm the induction of cancerous cachexia and the improvement effect of the complex extract, 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. In addition, in order to correct for the difference in body weight depending on the cancer tissue, the tumor weight after a total of 8 weeks of treatment and the total weight of the mice minus the cancer tissue weight (cancer free body weight) were compared. The weight change of subcutaneous fat (inguinal white adipose tissue, iWAT) and abdominal visceral fat (epididymal white adipose tissue, eWAT), which are white adipose tissue, was measured. The measurement results of each weight are as shown in FIG. 1 .
그 결과, 도 1에 나타난 바와 같이, 암이 비유발된 대조군(HFD)에서는 고지방식이 섭취에 의해 체중 및 백색지방조직 무게가 증가한 반면, 비만/암 동반 유발된 질병대조군(HFD+B16BL6 injection)에서는 전체 체중이 상대적으로 감소되는 것이 관찰되었으며, 특히, 암 조직을 제외한 체중 및 백색지방조직 무게가 대조군 대비 현저히 감소되어, 암성 악액질이 유발되었음을 확인하였다.As a result, as shown in FIG. 1 , in the non-cancerous control group (HFD), body weight and white adipose tissue weight increased by ingestion of a high-fat diet, whereas obesity/cancer-induced disease control group (HFD+B16BL6 injection) A relatively decreased overall body weight was observed, and in particular, the body weight excluding the cancer tissue and the weight of white adipose tissue were significantly reduced compared to the control group, confirming that cancerous cachexia was induced.
한편, 비만/암 동반질환 동물모델에서 실시예 1의 복합추출물(DD)을 처리하였을 때, 질병대조군 대비 암 조직의 무게(tumor weight)를 유의적으로(p<0.05)감소시켰으며, 이러한 감소는 항암제인 시스플라틴(CIS)과 유사한 수준의 효능을 보인 것으로 나타났다(도 1B). On the other hand, 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).
또한, 비만/암 동반질환 동물모델에서 실시예 1의 복합추출물(DD)을 처리하였을 때의 암 무게를 제외한 몸무게(tumor free body weight)는 질병대조군(HFD+B16BL6 injection)과 유사하게 측정되었지만, 항암제인 시스플라틴(CIS)을 처리하였을 때, 질병대조군에 비해 유의적으로(p<0.05) 감소되었다(도 1C). 특히, 복부내장지방(eWAT)의 경우 실시예 1의 복합추출물(DD)을 처리하였을 때, 질병대조군(HFD+B16BL6 injection) 대비 암 조직에 의한 지방 감소가 현저하게 억제되어, 대조군(HFD)과 거의 유사한 무게를 유지할 수 있음을 확인하였다(도 1E).In addition, 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 ). In particular, in the case of abdominal visceral fat (eWAT), 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).
결과적으로, 항암제인 시스플라틴은 암 조직 증가는 억제할 수 있으나, 암 조직에 의한 체중 감소 및 지방 감소는 억제할 수 없고 오히려 더 악화되는 반면, 본 발명의 실시예 1의 복합추출물(DD)은 시스플라틴과 유사한 항암 효과를 나타내면서도 암 조직에 의한 체중 감소 및 지방 감소를 현저히 억제함으로써, 암성 악액질에 대해 우수한 억제 효과를 나타냄을 확인하였다. As a result, the anticancer agent, cisplatin, can suppress the increase in cancer tissue, but cannot suppress the weight loss and fat loss caused by the cancer tissue, but rather worsens it, whereas 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 .
<실험예 3> 복합추출물의 암 세포사멸 지표 인자 발현에 대한 효과<Experimental Example 3> Effects of complex extracts on the expression of cancer apoptosis indicator factors
상기 동물 모델의 암 조직에서 본 발명의 실시예 1의 복합추출물(DD)이 세포사멸(apoptosis)인자 발현에 미치는 효과를 측정하기 위해, 미토콘드리아 내막 및 외막 단백질인 Bcl-family 중 대표적으로 Bcl-xl 및 Bax의 발현량 및 세포사멸의 주요 기전인 caspase cascade에서 대표적으로 caspase 3의 발현량의 변화를 웨스턴 블랏(Western blot)을 이용하여 확인하였다. 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.
상기 실험예 1 및 2에서 복합추출물(DD) 또는 시스플라틴(CIS)이 처리된 동물 모델의 암 조직 세포를 RIPA 버퍼 [50 mM Tris-HCl (pH 7.5), 0.1% 소듐 도데실 설페이트(sodium dodecyl sulphate, SDS), 0.1% Triton X-100, 1% Nonidet P-40, 0.5% 소듐 데옥시콜레이트(sodium deoxycholate), 150 mM NaCl 및 1 mM 페닐메틸설포닐 플루오라이드(phenylmethylsulphonyl fluoride)]로 용해시킨 후, 8% 소듐 도데실 설페이트-폴리아크릴아마이드 겔(sodium dodecyl sulfatepolyacrylamide gel) 전기 영동으로 분리하고 나이트로셀룰로스(nitrocellulose) 멤브레인으로 옮겼다. 멤브레인은 실온에서 1시간 동안 5% 탈지유가 함유된 TBST(10mM Tris, 150mM NaCl 및 0.05% Tween20, pH 7.6)로 블로킹하고, TBST로 세척 한 후, Bax, Bcl-xL, Caspase 3(Thermo Scientific, Waltham, MA, USA) 또는 액틴(β-actin, Santa Cruz Biotechnology, Inc.) 1차 항체와 함께 4℃에서 밤새동안 배양하였다. 이어서 멤브레인을 실온에서 2시간 동안 적절한 horseradish peroxidase (Jackson Lab.)가 부착된 2차 항체(Amersham Biosciences, Westborough, MA, USA)와 반응시켰다. 목적 단백질 밴드는 제조자의 지시에 따라 강화된 화학발광(enhanced chemiluminescence, ECL) 용액(Amersham Bioscience, Piscataway, NJ)을 사용하여 LAS 이미지 게이지(LAS Image Gauge) 프로그램에서 측정하였으며, 그 결과를 도 2에 나타내었다. 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. 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 (β-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.
그 결과, 도 2에 나타난 바와 같이, 질병대조군 대비 복합추출물(DD) 처리군에서 Bax/Bcl-xL의 비율이 증가되었고, 특히, cleaved/ pro caspase 3의 비율이 유의적으로 증가한 것으로 보아 caspase cascade 활성화에 의한 암 억제효과가 있는 것을 확인하였다.As a result, as shown in FIG. 2, 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.
이제까지 본 발명에 대하여 그 바람직한 실시예들을 중심으로 살펴보았다. 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자는 본 발명이 본 발명의 본질적인 특성에서 벗어나지 않는 범위에서 변형된 형태로 구현될 수 있음을 이해할 수 있을 것이다. 그러므로 개시된 실시예들은 한정적인 관점이 아니라 설명적인 관점에서 고려되어야 한다. 본 발명의 범위는 전술한 설명이 아니라 특허 청구범위에 나타나 있으며, 그와 동등한 범위 내에 있는 모든 차이점은 본 발명에 포함된 것으로 해석되어야 할 것이다.So far, the present invention has been looked at with respect to preferred embodiments thereof. Those of ordinary skill in the art to which the present invention pertains will understand that the present invention can be implemented in a modified form without departing from the essential characteristics of the present invention. Therefore, the disclosed embodiments are to be considered in an illustrative rather than a restrictive sense. The scope of the present invention is indicated in the claims rather than the foregoing description, and all differences within the scope equivalent thereto should be construed as being included in the present invention.

Claims (12)

  1. 단삼(Salviae Miltiorrhizae Radix) 및 대황(Rhei Radix et Rhizoma)의 복합추출물을 포함하는 악액질(cachexia) 예방 또는 치료용 약학적 조성물.A pharmaceutical composition for preventing or treating cachexia comprising a complex extract of Salviae Miltiorrhizae Radix and Rhubarb (Rhei Radix et Rhizoma).
  2. 제1항에 있어서, According to claim 1,
    상기 악액질은 암에 의해 유발되는 것인, 약학적 조성물.The cachexia is caused by cancer, the pharmaceutical composition.
  3. 제1항에 있어서, According to claim 1,
    상기 조성물은 식욕 감소, 체중 감소, 피로도 증가, 염증 증가, 근육 손실, 지방 손실 및 조혈 독성으로 이루어진 군에서 선택되는 1종 이상의 증상을 개선하는 것인, 약학적 조성물.The composition is 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.
  4. 제3항에 있어서,4. The method of claim 3,
    상기 조성물은 체중 감소 및 지방 손실로 이루어진 군에서 선택되는 1종 이상의 증상을 개선하는 것인, 약학적 조성물.The composition is to improve one or more symptoms selected from the group consisting of weight loss and fat loss, a pharmaceutical composition.
  5. 제1항에 있어서, According to claim 1,
    상기 조성물은 항암 효과 및 암성 악액질 억제 효과를 동시에 나타내는 것인, 약학적 조성물.The composition will exhibit the anticancer effect and the cancer cachexia inhibitory effect at the same time, the pharmaceutical composition.
  6. 제5항에 있어서,6. The method of claim 5,
    상기 항암 효과는 Bax 및 caspase 3로 이루어진 군으로부터 선택되는 1종 이상의 인자의 활성화를 통해 나타나는 것인, 약학적 조성물.The anticancer effect will appear through the activation of one or more factors selected from the group consisting of Bax and caspase 3, the pharmaceutical composition.
  7. 단삼 및 대황의 복합추출물을 포함하는 악액질 예방 또는 개선용 건강기능식품 조성물.A health functional food composition for preventing or improving cachexia comprising a complex extract of ginseng and rhubarb.
  8. 제7항에 있어서, 8. The method of claim 7,
    상기 악액질은 암에 의해 유발되는 것인, 건강기능식품 조성물.The cachexia is a health functional food composition that is caused by cancer.
  9. 단삼 및 대황의 복합추출물을 포함하는 악액질 예방 또는 개선용 건강식품 조성물.A health food composition for preventing or improving cachexia comprising a complex extract of ginseng and rhubarb.
  10. 제9항에 있어서, 10. The method of claim 9,
    상기 악액질은 암에 의해 유발되는 것인, 건강식품 조성물.The cachexia is caused by cancer, health food composition.
  11. 제1항의 악액질 예방 또는 치료용 약학적 조성물을 포함하는 항암 보조제 조성물.An anticancer adjuvant composition comprising the pharmaceutical composition for preventing or treating cachexia of claim 1 .
  12. 제1항의 악액질 예방 또는 치료용 약학적 조성물을 환자에게 투여하는 것을 포함하는 암 및 악액질 예방 또는 치료 방법.A method for preventing or treating cancer and cachexia comprising administering the pharmaceutical composition for the prevention or treatment of cachexia of claim 1 to a patient.
PCT/KR2020/015608 2020-11-09 2020-11-09 Composition for preventing or treating cachexia, containing complex extract of salviae miltiorrhizae radix and rhei radix et rhizoma WO2022097794A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/KR2020/015608 WO2022097794A1 (en) 2020-11-09 2020-11-09 Composition for preventing or treating cachexia, containing complex extract of salviae miltiorrhizae radix and rhei radix et rhizoma
JP2023527759A JP2023548411A (en) 2020-11-09 2020-11-09 A composition for preventing or treating cachexia containing a complex extract of Danjin and Rhubarb

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/KR2020/015608 WO2022097794A1 (en) 2020-11-09 2020-11-09 Composition for preventing or treating cachexia, containing complex extract of salviae miltiorrhizae radix and rhei radix et rhizoma

Publications (1)

Publication Number Publication Date
WO2022097794A1 true WO2022097794A1 (en) 2022-05-12

Family

ID=81456768

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2020/015608 WO2022097794A1 (en) 2020-11-09 2020-11-09 Composition for preventing or treating cachexia, containing complex extract of salviae miltiorrhizae radix and rhei radix et rhizoma

Country Status (2)

Country Link
JP (1) JP2023548411A (en)
WO (1) WO2022097794A1 (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009004390A (en) * 2008-10-03 2009-01-08 Sony Corp Fluorescent lamp, and display device
KR20120040026A (en) * 2010-10-18 2012-04-26 동국대학교 경주캠퍼스 산학협력단 Pharmaceutical composition for preventing and treatmenting containing of salvia miltiorrhiza from disease related to renal failure
JP5300195B2 (en) * 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 Composition of botanical extract for cancer treatment
KR102146463B1 (en) * 2018-10-18 2020-08-21 한명석 Composition for improving muscular quality comprising Eisenia bicyclis extract or its fraction

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5300195B2 (en) * 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 Composition of botanical extract for cancer treatment
JP2009004390A (en) * 2008-10-03 2009-01-08 Sony Corp Fluorescent lamp, and display device
KR20120040026A (en) * 2010-10-18 2012-04-26 동국대학교 경주캠퍼스 산학협력단 Pharmaceutical composition for preventing and treatmenting containing of salvia miltiorrhiza from disease related to renal failure
KR102146463B1 (en) * 2018-10-18 2020-08-21 한명석 Composition for improving muscular quality comprising Eisenia bicyclis extract or its fraction

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHEN LINLIN; YANG QUANJUN; ZHANG HONG; WAN LILI; XIN BO; CAO YAN; ZHANG JUNPING; GUO CHENG: "Cryptotanshinone prevents muscle wasting in CT26-induced cancer cachexia through inhibiting STAT3 signaling pathway", JOURNAL OF ETHNOPHARMACOLOGY, ELSEVIER IRELAND LTD, IE, vol. 260, 4 June 2020 (2020-06-04), IE , XP086243640, ISSN: 0378-8741, DOI: 10.1016/j.jep.2020.113066 *
LEE, JI EUN;CHOI, JIN YONG;HAN, CHANG WOO;CHOI, JUN YONG;PARK, SEONG HA;KIM, SO YEON;: "A Review on Experimental Research about Anticancer Drug Combined Treatment with Herbal Medicine for Killing or Inhibiting Proliferation of Cancer cells in Korea.", KOREAN JOURNAL OF ORIENTAL MEDICAL PRESCRIPTION, KOREAN INTELLECTUAL PROPERTY OFFICE, KR, vol. 25, no. 3, 31 August 2017 (2017-08-31), KR , pages 391 - 412, XP053036340, ISSN: 1229-1218 *

Also Published As

Publication number Publication date
JP2023548411A (en) 2023-11-16

Similar Documents

Publication Publication Date Title
US20100316741A1 (en) Composition comprising the extract of crude drug complex for stimulating bone growth
KR20120119160A (en) Composition comprising an extract of curcuma longa l. or curcuma aromatica l. isolated therefrom having il-6 induced stat3 inhibitory activity
WO2017014502A1 (en) Pharmaceutical composition for preventing or treating il-6-mediated diseases comprising rosa rugosa flower extract as active ingredient
KR20210122167A (en) Composition for Preventing, Improving or Treating Postmenopausal Syndrome Comprising Rosa rugosa Thunberg Extract
KR102187335B1 (en) Composition for improving premenstrual syndrome symptom comprising compounds isolated from Hordeum vulgare extract
WO2022097794A1 (en) Composition for preventing or treating cachexia, containing complex extract of salviae miltiorrhizae radix and rhei radix et rhizoma
WO2020241958A1 (en) Composition for preventing or treating woman menopause symptoms, comprising cordyceps militaris concentrate as active ingredient
WO2022098192A1 (en) Composition for preventing or treating cachexia comprising medicinal herb complex extract
WO2018008973A1 (en) Composition comprising forsythiae fructus extract as effective ingredient for preventing, ameliorating or treating peripheral neuropathy
WO2014133286A1 (en) Composition containing extracts of artemisia iwayomogi and curcuma longa as active ingredients for preventing, inhibiting, or treating obesity-related diseases
WO2017142371A1 (en) Composition containing phragmitis rhizoma extract as active ingredient for preventing, ameliorating, or treating disease attributed to side effect of anticancer agent
KR102512655B1 (en) Composition for preventing or treating cachexia comprising complex extract of Salviae Miltiorrhizae Radix and Rhei Radix et Rhizoma
WO2020122385A1 (en) Composition comprising elecampane extract for alleviating premenstrual syndrome symptom
KR20140114950A (en) A composition comprising Amomum cardamomum L. extracts having anti-obesity activity
WO2021132897A1 (en) Composition for prevention, amelioration, or treatment of cancer cachexia comprising piperine
JP2021054838A (en) Composition comprising oleanolic acid acetate as active ingredient for preventing, alleviating or treating renal toxicity induced by medicine
WO2022119193A1 (en) Composition, for preventing, relieving or treating cancer cachexia, containing uchasingi-hwan
KR20150113434A (en) A composition comprising the extract of ginseng seed for protecting brain cells and preventing, improving and treating depression
WO2024080420A1 (en) Composition for preventing and treating liver cancer containing ginsenoside rh2 and ginsenoside rg5 as active ingredients
KR20200089527A (en) Composition comprising extracts of Acorus gramineus and Dendropanax morbifera for anti-inflammation
KR102298385B1 (en) Composition containing vanillic acid for preventing, improving or treating cancer cachexia
WO2021187679A1 (en) Composition, comprising sea cucumber-derived saponin compound, for preventing, alleviating, or treating neuropathy
WO2024010394A1 (en) Composition for ameliorating or treating cancer cachexia containing calcium lactate as active ingredient
KR102096345B1 (en) Composition for preventing, improving or treating vasculitis comprising Curcuma zedoaria extract as effective component
KR102464897B1 (en) Herbal Compositions for Prevention, Improvement or Treatment of Benign Prostatic Hyperplasia

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 20960894

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2023527759

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 20960894

Country of ref document: EP

Kind code of ref document: A1