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WO2022098192A1 - Composition pour la prévention ou le traitement de la cachexie comprenant un extrait complexe de plantes médicinales - Google Patents

Composition pour la prévention ou le traitement de la cachexie comprenant un extrait complexe de plantes médicinales Download PDF

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Publication number
WO2022098192A1
WO2022098192A1 PCT/KR2021/016150 KR2021016150W WO2022098192A1 WO 2022098192 A1 WO2022098192 A1 WO 2022098192A1 KR 2021016150 W KR2021016150 W KR 2021016150W WO 2022098192 A1 WO2022098192 A1 WO 2022098192A1
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cancer
cachexia
composition
preventing
present
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English (en)
Korean (ko)
Inventor
엄재영
안광석
양웅모
이석근
정윤우
박진봉
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Kyung Hee University
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Kyung Hee University
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/89—Cyperaceae (Sedge family)
    • A61K36/8905—Cyperus (flatsedge)
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • 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
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/308—Foods, ingredients or supplements having a functional effect on health having an effect on cancer prevention
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • the present invention relates to a composition for preventing, improving or treating cachexia comprising a herbal medicine complex extract, and more particularly, for preventing, improving or treating cancerous cachexia comprising a complex extract of Cyperi Rhizoma and Zanthoxyli Pericarpium It relates to pharmaceutical compositions, health functional food compositions, and anticancer adjuvant compositions.
  • 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.
  • Cyperi Rhizoma is a rhizome of Cyperus rotundus Linne belonging to the Cyperaceae and is an herbal medicine meaning that the thin root is removed. It is known to improve blood circulation and is widely used for menstrual irregularities, menstrual pain, and gynecological diseases before and after childbirth. In addition, it is prescribed as an antipyretic, sedative and digestive, and is used for colds, headaches, abdominal pain, and loss of appetite.
  • Zanthoxyli Pericarpium is the dried pericarp of the ripe fruit of Zanthoxylum piperitum AP Dc. belonging to the Rutaceae family. In oriental medicine, it is used to relieve cold energy by acting on the spleen, stomach, and kidneys because it has a hot and spicy taste, and is used to relieve pain.
  • the present inventors found that the complex extracts of Hyangbuja and Cheoncho, which are natural products, have significant anticancer and cancerous cachexia improvement effects by inhibiting weight loss and fat loss caused by cancer in an animal model of obesity/cancer comorbidity, and inducing cancer cell death. 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 cancer and cachexia.
  • the present invention provides a pharmaceutical composition for preventing or treating cachexia comprising a complex extract of Cyperi Rhizoma and Zanthoxyli Pericarpium.
  • 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 hyangbuja and cheoncho.
  • 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 cancer and cachexia, comprising administering the pharmaceutical composition for preventing or treating cachexia to a patient.
  • the complex extract of Hyangbuja and Cheoncho 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, thereby exhibiting significant anticancer and cancerous cachexia improvement effects. It may be useful as a composition for preventing, improving or treating cancerous cachexia, which can simultaneously improve anti-cancer treatment and cachexia without side effects.
  • FIG. 1 shows the body weight change (body weight change) for 7 weeks in an animal model of obesity/cancer comorbidity according to the treatment with the complex extract of Hyangbuja and cheoncho of the present invention.
  • Figure 3 shows the effect on the expression of cancer apoptosis-related factors (Bcl-xl, Bax, cleaved-caspase 3 and caspase 3) of the complex extract of Hyangbuja and Cheoncho.
  • the present invention provides a pharmaceutical composition for preventing or treating cachexia comprising a complex extract of Cyperi Rhizoma and Zanthoxyli Pericarpium.
  • the hyangbuja (Cyperi Rhizoma) is a rhizome of Cyperus rotundus Linne belonging to the Cyperaceae, and the thin root is removed.
  • the cheoncho (Zanthoxyli Pericarpium, Stream) is the dried pericarp of the ripe fruit of Zanthoxylum piperitum AP Dc. belonging to the Rutaceae family.
  • 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 exhibited through the activation of one or more factors selected from the group consisting of Bax and caspase 3, and thus may exhibit a cancer cell death effect.
  • the complex extract of Hyangbuja and Cheoncho 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 Hyangbuja and Cheoncho of the present invention is significantly increased compared to each single extract.
  • the complex extract of Hyangbuja and Cheoncho may be obtained by extracting a mixture of Hyangbuja and Cheoncho, or may be a mixture of a single extract obtained by extracting each of Hyangbuja and Cheoncho, but is not limited thereto.
  • extract refers to a preparation concentrated by squeezing the extraction target with an appropriate leachate and evaporating the leachate. 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 comprises the steps of mixing Hyangbuja and Cheoncho; 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.
  • the extraction may be performed by adding the extraction solvent in an amount of 1 to 10 times the weight of the mixture of Hyangbuja and Cheoncho.
  • 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 hyangbuja and cheoncho 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 Hyangbuja and Cheoncho of the present invention may be administered in various oral and parenteral formulations during clinical administration, and in the case of formulation, commonly used fillers, extenders, binders, wetting agents, disintegrants, diluents such as surfactants, etc. or using an excipient.
  • Solid preparations for oral administration include tablets, patients, powders, granules, capsules, troches, etc., and these solid preparations include at least one excipient, 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 dosage for the human body of the complex extract of Hyangbuja and Cheoncho 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 Hyangbuja (Cyperi Rhizoma) and Zanthoxyli Pericarpium.
  • the present invention provides a health food composition for preventing or improving cachexia comprising a complex extract of Hyangbuja (Cyperi Rhizoma) and Zanthoxyli Pericarpium.
  • 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 Hyangbuja and Cheoncho 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 may be added to health functional food or health food, such as food and beverage, for the purpose of preventing or improving cancerous cachexia.
  • Examples of foods to which the complex extract of Hyangbuja and Cheoncho according to the present invention can be added include drinks, meat, sausages, 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 Hyangbuja and Cheoncho 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 hyangbuja and cheoncho 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 Hyangbuja and cheoncho according to the present invention as an essential ingredient 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.
  • the health food and health functional food composition containing the complex extract of Hyangbuja and Cheoncho 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 anti-cancer adjuvant composition may further include one or more active ingredients exhibiting the same or similar functions in addition to including the complex extract of Hyangbuja and Cheoncho 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 cancer and 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 Hyangbuja (Cyperi Rhizoma) and Zanthoxyli Pericarpium was prepared by hot water extraction by mixing Hyangbuja and Chuncho in a weight ratio of 1:1. Specifically, after cleaning and washing the medicinal herbs of Hyangbuja and Cheoncho, 250 g of Hyangbuja and 250 g of Cheoncho were mixed, put in 1 L of distilled water, and heated at 100° C. for 2 hours to make 500 ml. The Jeontang solution was freeze-dried to prepare a powdered hyangbuja and cheoncho complex extract (Example 1, HC).
  • the body weight change of the mice was measured during the treatment period for a total of 7 weeks in the same manner as in Example 1, and is shown in FIG.
  • total body weight, cancer weight, white adipose tissue (inguinal white adipose tissue, iWAT) and abdomen after a total of 7 weeks of treatment The weights of visceral fat (epididymal white adipose tissue, eWAT) were respectively measured and compared. The measurement results of each weight are shown in FIG. 2 .
  • the body weight of the control group (HFD+B16BL6 injection) compared to the control group (HFD) in the animal model of obesity/cancer comorbidity was significantly reduced by 16%, whereas the complex extract (HC) of Example 1 was treated.
  • This weight loss was suppressed and increased to a level similar to that of the control group (FIG. 2A).
  • iWAT subcutaneous fat
  • eWAT abdominal visceral fat
  • Example 2 when the complex extract (HC) of Example 1 was treated in the animal model of obesity/cancer comorbidity, the weight of cancer tissue compared to the disease control group was significantly (p ⁇ 0.05) reduced (Fig. 2B) .
  • 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 (HC) of Example 1 of the present invention is excellent It was confirmed that, while exhibiting an anticancer effect, it significantly inhibited weight loss and fat loss caused by cancer tissue, thereby exhibiting an excellent inhibitory effect on cancerous cachexia.
  • Example 1 of the present invention In order to measure the effect of the complex extract (HC) 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.
  • HC complex extract
  • the cancer tissue cells of the animal model were treated with RIPA buffer [50 mM Tris-HCl (pH 7.5), 0.1% 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], followed by 8% sodium dodecyl sulfate-polyacrylamide gel electrolysis It was separated by electrophoresis and transferred to a nitrocellulose membrane.
  • RIPA buffer 50 mM Tris-HCl (pH 7.5), 0.1% 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
  • 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. 3 indicated.
  • ECL enhanced chemiluminescence

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Abstract

La présente invention concerne une composition destinée à prévenir, à soulager ou à traiter la cachexie, contenant un extrait complexe de Cyperi rhizoma et de Zanthoxyli pericarpium. L'extrait complexe de la présente invention a pour effet de supprimer la perte de poids et la perte de graisse provoquée par le cancer et d'induire la mort des cellules cancéreuses, et peut donc être utile en tant que composition destinée à prévenir, à soulager ou à traiter la cachexie cancéreuse, la composition permettant simultanément un traitement anticancéreux sans effets secondaires de type cachexie et une amélioration de la cachexie.
PCT/KR2021/016150 2020-11-09 2021-11-08 Composition pour la prévention ou le traitement de la cachexie comprenant un extrait complexe de plantes médicinales Ceased WO2022098192A1 (fr)

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JP2009046391A (ja) * 2005-07-06 2009-03-05 Takehito Kono 悪液質改善治療製剤および悪液質改善作用を有する食品製剤
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KR20200001730A (ko) * 2018-06-28 2020-01-07 차의과학대학교 산학협력단 김치를 포함하는 악액질 예방, 개선 또는 치료용 조성물

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