Method for producing a composition for preventing or treating cachexia containing a combined extract of Salvia miltiorrhiza and Rhubarb

Abstract

The present invention relates to a composition for preventing, ameliorating, or treating cachexia, comprising a combined extract of Danshen and Rhubarb. The combined extract may be useful as a composition for preventing, ameliorating, or treating cancer cachexia, which can simultaneously provide anti-cancer treatment and improve cachexia without cachexia side effects by suppressing weight loss and fat loss caused by cancer and inducing cancer cell death.

Description

[Technical Field]

[0001] The present invention relates to a composition for preventing, ameliorating or treating cachexia, comprising a complex extract of traditional Chinese medicine, and more particularly to a pharmaceutical composition, a health functional food composition and an anti-cancer supplement composition for preventing, ameliorating or treating cancer-related cachexia, comprising a complex extract of Danshen (Salviae Miltiorrhizae Radix) and Rhei Radix et Rhizoma. [Background technology]

[0002] Cachexia is a complex syndrome characterized by persistent muscle loss due to various diseases, including cancer, heart failure, chronic obstructive pulmonary disease, chronic kidney disease, and acquired immune deficiency syndrome (AIDS). Cancer cachexia is a complex metabolic syndrome associated with malignant tumors, defined as a loss of 5% or more of body weight due to muscle and fat loss within six months of the onset of cancer. Cachexia can occur in a variety of medical conditions, and cancer cachexia is closely related to terminal cancer. Approximately 50% of all cancer patients, and especially approximately 80% of terminal cancer patients, are affected by cancer cachexia, suffering from reduced quality of life and increased mortality due to muscle and / or fat loss. Cancer cachexia is characterized by weight loss through significant loss of muscle mass and / or adipose tissue, and is distinct from muscle and fat loss due to appetite suppression.

[0003] Treatments for cancer cachexia include NSAIDs (non-steroidal anti-inflammatory drugs), β2-adrenergic agonists, corticosteroids, and ghrelin, and the drugs most commonly used to treat cancer cachexia on the market to date are COX-2 inhibitors and TNF-α inhibitors.

[0004] COX-2 inhibitors are drugs that reduce skeletal muscle loss by inhibiting COX-2, which is involved in the production of prostaglandins, inflammatory substances produced in large quantities in cancer tissue. Celecoxib is available commercially as a COX-2 inhibitor. However, celecoxib has been reported to cause side effects such as anemia, stomach ulcers, allergies, heart attacks, and strokes.

[0005] TNF-α inhibitors are drugs that kill cancer cells by reducing the expression of TNF-α, which is highly expressed in the serum of patients with cancer cachexia. Thalidomide is a TNF-α inhibitor available on the market. However, these drugs are not very effective in treating cancer cachexia and have side effects such as depression, heart failure, shortness of breath, vomiting, rash, high blood pressure, and birth defects during pregnancy.

[0006] As such, most of the drugs currently under development or on the market have many side effects and lack evidence of their therapeutic effects. Therefore, there is a pressing need for the development of cancer cachexia treatments with new mechanisms.

[0007] Meanwhile, Danshen (Salviae Miltiorrhizae Radix) is a traditional Chinese medicine derived from the roots of Danshen (Salvia miltiorrhiza Bunge), which belongs to the mint family (Lamiaceae), and has been shown to have effects on the cardiovascular system and various vascular diseases, inhibit damage to the liver, lungs, and kidneys, be active against osteoporosis, and have central nervous system effects, as well as anti-inflammatory, antioxidant, and anti-cancer effects.

[0008] Rheum palmatum (Rhei Radix et Rhizoma) is the root and rhizome of the perennial herbaceous plant Rheum palmatum Linne, Rheum tanguticum Maximowicz ex Balf., or Rheum officinale Baillon, which belongs to the Polygonaceae family, with the integument removed. It is clinically used to treat indigestion, constipation, acute inflammation, infectious diseases, parasitic diseases, bleeding, thrombocytopenia, burns, and skin diseases.

[0009] The present inventors have confirmed that a combined extract of the natural products Danshen and Rhubarb suppresses cancer-induced weight loss and fat loss in an animal model of obesity / cancer-associated disease, induces cancer cell death, and has significant anti-cancer and cancer cachexia-improving effects, thereby completing the present invention. Summary of the Invention [Problem to be solved by the invention]

[0010] An object of the present invention is to provide a pharmaceutical composition for preventing or treating cachexia.

[0011] Another object of the present invention is to provide a health functional food composition and a health food composition for preventing or improving cachexia.

[0012] It is yet another object of the present invention to provide an anti-cancer adjuvant composition comprising the pharmaceutical composition.

[0013] It is yet another object of the present invention to provide a method for preventing or treating cachexia. [Means for solving the problem]

[0014] To achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating cachexia, comprising a combined extract of Danshen (Salviae Miltiorrhizae Radix) and Rhei Radix et Rhizoma.

[0015] In one embodiment of the present invention, the cachexia may be cancer-induced.

[0016] The present invention also provides a functional health food composition and a health food composition for preventing or improving cachexia, which contain a combined extract of Salvia miltiorrhiza and Rhubarb.

[0017] Furthermore, the present invention provides an anti-cancer adjuvant composition comprising the pharmaceutical composition for preventing or treating cachexia.

[0018] Furthermore, the present invention provides a method for preventing or treating cachexia, which comprises administering the pharmaceutical composition for preventing or treating cachexia to a patient. [Effects of the Invention]

[0019] The combined extract of Danshen and Rhubarb of the present invention exhibits significant anti-cancer and cancer cachexia-improving effects by suppressing cancer-induced weight loss and fat loss in an animal model of obesity / cancer-associated disease and inducing cancer cell death through caspase cascade activation. Therefore, it may be useful as a composition for preventing, improving, or treating cancer cachexia, which can simultaneously provide anti-cancer treatment and improve cachexia without cachexia side effects. [Brief explanation of the drawings]

[0020] [Figure 1]1 shows the results of measuring changes in body weight, tumor weight, cancer-free body weight (the weight of the whole mouse minus the weight of the cancer tissue), subcutaneous fat (inguinal white adipose tissue, iWAT), and abdominal visceral fat (epididymal white adipose tissue, eWAT) in an animal model of obesity / cancer-associated disease treated with a combined extract of Danshen and Rhubarb of the present invention. [Figure 2] The effect of a combined extract of Danshen and Rhubarb on the expression of cancer cell death-related factors (Bcl-xl, Bax, cleaved-caspase 3, and caspase 3) is shown. DETAILED DESCRIPTION OF THE INVENTION

[0021] The present invention will be described in detail below.

[0022] Pharmaceutical composition for preventing or treating cachexia The present invention provides a pharmaceutical composition for preventing or treating cachexia, comprising a combined extract of Danshen (Salviae Miltiorrhizae Radix) and Rhubarb (Rhei Radix et Rhizoma).

[0023] The term "cachexia," as used herein, refers to a severe generalized debilitating symptom seen in the terminal stages of cancer, tuberculosis, diabetes, acquired immunodeficiency syndrome (AIDS), and other conditions. It is commonly seen in patients with gastrointestinal cancers, such as stomach cancer, esophageal cancer, pancreatic cancer, and colon cancer, as well as lung cancer. It manifests with symptoms such as loss of appetite, weight and physical strength due to muscle and fat loss, anemia, lethargy, and indigestion, and particularly refers to a condition in which weight loss occurs despite normal food intake. Cachexia can lead to poor responses to anticancer chemotherapy and radiation therapy, reducing patients' quality of life and life expectancy, and causing death due to weight loss in 10 to 20% of all cancer patients.

[0024] In the pharmaceutical composition according to the present invention, the cachexia may be induced by cancer. In one embodiment of the present invention, the cachexia induced by cancer is referred to as "cancer cachexia."

[0025] Cancer as defined in this application may include melanoma, leukemia, lymphoma, myeloma, myelodysplastic syndrome, breast cancer, head and neck cancer, esophageal cancer, gastric cancer, colorectal cancer (= colon cancer), rectal cancer, anal cancer, hepatocellular carcinoma, bile duct cancer, gallbladder cancer, pancreatic cancer, lung cancer (non-small cell lung cancer, small cell lung cancer), thymic cancer, kidney cancer, bladder cancer, prostate cancer, testicular cancer, ovarian cancer, cervical cancer, sarcoma, gastrointestinal stromal tumor (GIST), carcinoma of unknown origin, mesothelioma, neuroendocrine tumor, skin cancer, blood cancer, etc.

[0026] The pharmaceutical 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, and preferably improves one or more symptoms selected from the group consisting of weight loss and fat loss.

[0027] The pharmaceutical composition according to the present invention may simultaneously exhibit anti-cancer effects and anti-cancer cachexia effects.

[0028] The anti-cancer effect may be exhibited through activation of one or more factors selected from the group consisting of Bax and caspase 3. Preferably, the anti-cancer effect may be exhibited through activation of a caspase cascade.

[0029] According to one embodiment of the present invention, a combined extract of Danshen and Rhubarb showed the effect of improving weight loss and fat loss caused by cancer tissue in an animal model of obesity / cancer-associated disease, and also showed the effect of activating the expression of Bax and caspase 3, which act as factors for cancer cell death, and the effect of suppressing cancer, thereby confirming the effect of improving cancer cachexia as well as the anti-cancer effect (see Experimental Examples 1 to 3).

[0030] The above-mentioned effects may be significantly enhanced by the combined extract of Salvia miltiorrhiza and Rhubarb of the present invention compared to the respective extracts alone.

[0031] In the present invention, the composite extract of Salvia miltiorrhiza and Rhubarb may be an extract of a mixture of Salvia miltiorrhiza and Rhubarb, or a mixture of extracts of Salvia miltiorrhiza and Rhubarb, respectively, but is not limited thereto.

[0032] The term "extract" refers to a preparation obtained by squeezing a target substance with an appropriate infusion solution and evaporating the infusion solution to concentrate it, and may be, but is not limited to, an extract obtained by extraction treatment, a diluted or concentrated extract, a dried product obtained by drying the extract, or a crude or purified product thereof. The extraction method is not limited to, but preferably, methods such as hot water extraction, hot water extraction, cold maceration extraction, reflux cooling extraction, or ultrasonic extraction can be used.

[0033] For example, the composite extract may be prepared by a method including, but not limited to, mixing Salvia miltiorrhiza and Rhubarb; and steeping the mixture in water, a C1-C4 alcohol, ethyl acetate, or a mixture thereof to obtain an extract. The C1-C4 alcohol may be ethanol, methanol, butanol, or a combination thereof. The extraction solvent may be added in an amount of 1 to 10 times the volume of the Salvia miltiorrhiza and Rhubarb mixture. The extraction temperature may be, but is not limited to, 30 to 120°C. The extraction time may be, but is not limited to, 2 to 48 hours.

[0034] The Salvia miltiorrhiza and Rhubarb may be mixed in a weight ratio of 0.1:10 to 10:0.1, preferably in a weight ratio of 0.5:5 to 5:0.5, more preferably in a weight ratio of 1:3 to 3:1, and most preferably in a weight ratio of 1:2 to 2:1.

[0035] The extraction method may further include fractionating the extract with water, a C1 to C4 alcohol, or a combination thereof. Preferably, the extract may be fractionated with water, ethanol, methanol, butanol, ethyl acetate, hexane, or a combination thereof. The extraction method may further include concentrating, centrifuging, filtering, adsorbing, or subjecting the extract to chromatography.

[0036] The pharmaceutical compositions according to the present invention may be formulated for oral, intramuscular, intravenous, intraperitoneal, subcutaneous, intradermal, or topical administration.

[0037] The compound extract of Salvia miltiorrhiza and Rhubarb of the present invention may be administered in various oral and parenteral dosage forms in clinical administration, and when formulated, it is prepared using commonly used diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, etc.

[0038] Solid formulations for oral administration include tablets, pills, powders, granules, capsules, and lozenges. These solid formulations are prepared by mixing one or more of the present Danshen and Rhubarb complex extracts with at least one excipient, such as starch, calcium carbonate, sucrose, lactose, or gelatin. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid formulations for oral administration include suspensions, oral solutions, emulsions, and syrups. In addition to commonly used diluents such as water and liquid paraffin, various excipients, such as wetting agents, sweeteners, flavoring agents, and preservatives, may be included.

[0039] Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, suppositories, etc. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases may include witepsol, macrogol, Tween 61, cocoa butter, laurin butter, glycerol, gelatin, etc.

[0040] The pharmaceutical composition may further comprise a carrier, excipient, or diluent, such as lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, or mineral oil.

[0041] In addition, the pharmaceutical composition may further contain a known active ingredient having cancer cachexia prevention or treatment activity.

[0042] The effective dosage of the Danshen and Rhubarb complex extract of the present invention for humans varies depending on the patient's age, weight, sex, dosage form, health condition, and disease severity, but is generally about 0.001 to 100 mg / kg / day, preferably 0.01 to 35 mg / kg / day. For an adult patient weighing 70 kg, the dosage is generally 0.07 to 7000 mg / day, preferably 0.7 to 2500 mg / day, and may be administered once or several times a day at regular intervals according to the doctor's or pharmacist's judgment.

[0043] Health functional food and health food composition for preventing or improving cachexia The present invention also provides a health functional food composition for preventing or improving cachexia, which comprises a complex extract of Danshen (Salviae Miltiorrhizae Radix) and Rhubarb (Rhei Radix et Rhizoma).

[0044] Furthermore, the present invention provides a health food composition for preventing or improving cachexia, which comprises a combined extract of Danshen (Salviae Miltiorrhizae Radix) and Rhubarb (Rhei Radix et Rhizoma).

[0045] In the functional health food composition or health food composition according to the present invention, the cachexia may be induced by cancer.

[0046] The functional health 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, and preferably improve one or more symptoms selected from the group consisting of weight loss and fat loss.

[0047] The functional health food composition or health food composition according to the present invention may simultaneously exhibit an anti-cancer effect and an effect of suppressing cancer cachexia.

[0048] The anti-cancer effect may be exhibited through activation of one or more factors selected from the group consisting of Bax and caspase 3. Preferably, the anti-cancer effect may be exhibited through activation of a caspase cascade.

[0049] According to one embodiment of the present invention, a combined extract of Danshen and Rhubarb showed the effect of improving weight loss and fat loss caused by cancer tissue in an animal model of obesity / cancer-associated disease, and also showed the effect of activating the expression of Bax and caspase 3, which act as factors for cancer cell death, and the effect of suppressing cancer, thereby confirming the effect of improving cancer cachexia as well as the anti-cancer effect (see Experimental Examples 1 to 3).

[0050] The term "health functional food" as used herein refers to a food product manufactured and processed in the form of tablets, capsules, pills, liquids, powders, granules, etc. using raw materials or ingredients that have beneficial functions for the human body. Here, "functional" refers to the regulation of nutrients for the structure and function of the human body or the attainment of beneficial health effects, such as physiological effects. The health functional food product of the present invention can be manufactured using methods commonly used in the art, and can be manufactured using raw materials and ingredients commonly used in the art. Furthermore, the dosage form of the health functional food product of the present invention can be any dosage form recognized as a health functional food. The health functional food composition of the present invention can be manufactured in various dosage forms, and unlike common pharmaceuticals, it has the advantage of being made from food ingredients, eliminating side effects that can occur with long-term drug administration, and is highly portable. The health functional food product of the present invention can be taken as an adjuvant to enhance the effects of cancer cachexia treatments or anticancer drugs.

[0051] The health functional food composition or health food composition according to the present invention can be added to health functional foods or health foods such as foods and beverages by adding the complex extract of Danshen and Rhubarb for the purpose of preventing or improving cancer cachexia.

[0052] The type of food is not particularly limited. Examples of foods to which the Danshen and Rhubarb complex extract according to the present invention can be added include drinks, meat, sausages, bread, biscuits, rice cakes, chocolate, candies, snacks, sweets, pizza, ramen, other noodles, chewing gum, dairy products including ice cream, various soups, drinking water, alcoholic beverages, vitamin complexes, dairy products and dairy products, etc., and include all health foods and health functional foods in the usual sense.

[0053] The functional health food and health food composition according to the present invention may be added directly to food or used with other foods or food ingredients, and may be used appropriately in a conventional manner. The amount of the Danshen and Rhubarb complex extract according to the present invention may be appropriately determined depending on the intended use (prevention or improvement). Generally, the amount of the Danshen and Rhubarb complex extract in health foods and functional health foods may be 0.1 to 90 parts by weight of the total food. However, in the case of long-term intake for the purpose of health maintenance or health regulation, the amount may be less than the above range, and since there is no safety issue, the effective ingredients may be used in amounts greater than the above range.

[0054] The health food and health functional food compositions of the present invention contain the Salvia miltiorrhiza and Rhubarb complex extract of the present invention as an essential ingredient in the indicated proportions, but other ingredients are not particularly limited. Similar to conventional beverages, they may contain various flavorings or natural carbohydrates as additional ingredients. Examples of the natural carbohydrates mentioned above include monosaccharides such as glucose and fructose; disaccharides such as maltose and sucrose; and polysaccharides such as common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. Other flavorings that can be advantageously used include natural flavorings (thaumatin, stevia extract (e.g., rebaudioside A, glycyrrhizin), and synthetic flavorings (saccharin, aspartame, etc.). The proportion of the natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g, per 100 g of the health functional food composition of the present invention.

[0055] In addition to the above, the health food and health functional food compositions containing the Danshen and Rhubarb composite extract of the present invention may contain various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and fillers (cheese, chocolate, etc.), pectinic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonation agents used in carbonated beverages, etc. In addition, the health food and health functional food compositions of the present invention may contain natural fruit juices and fruit pulp for producing fruit juice drinks and vegetable drinks.

[0056] These ingredients can be used independently or in combination. The proportion of such additives is not limited thereto, but is generally selected from the range of 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.

[0057] Anticancer adjuvant composition The present invention also provides an anti-cancer adjuvant composition comprising the pharmaceutical composition for preventing or treating cachexia according to the present invention.

[0058] The term "anticancer adjuvant" as used in the present invention can be used to enhance the anticancer therapeutic effect and suppress or ameliorate the side effects of an anticancer drug, and can be administered to a patient in combination with an anticancer drug.

[0059] The anticancer adjuvant composition of the present invention may exhibit an effect of suppressing or improving cachectic symptoms such as muscle loss, weight loss, fat loss, hematopoietic toxicity, and appetite loss induced by cancer, thereby enhancing the anticancer effect of an anticancer drug.

[0060] Existing anti-cancer drugs as defined in the present application may include cisplatin, cyclophosphamide, methotrexate, 5-fluorouracil, doxorubicin, mustine, vincristine, procarbazine, prednisolone, bleomycin, vinblastine, dacarbazine, etoposide, epirubicin, cisplatin, capecitabine, oxaliplatin, and the like.

[0061] The anti-cancer adjuvant composition may contain, as an active ingredient, a composite extract of Danshen and Rhubarb, and may further contain one or more active ingredients exhibiting the same or similar functions. The anti-cancer adjuvant may be administered orally or parenterally in clinical administration. For parenteral administration, it may be administered by intraperitoneal injection, intrarectal injection, subcutaneous injection, intravenous injection, intramuscular injection, endometrial injection, intracerebrovascular injection, or intrathoracic injection, and may be used in the form of a general pharmaceutical formulation.

[0062] The anticancer adjuvant may be used alone or in combination with 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, administered once or several times daily in divided doses. The range varies depending on the patient's weight, age, sex, health condition, diet, administration time, administration method, excretion rate, and disease severity. The anticancer adjuvant of the present invention may be administered in various parenteral dosage forms during clinical administration. When formulated, it is typically prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspending agents that can be used include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.Suppository bases that can be used include witepsol, macrogol, Tween 61, cacao butter, laurin butter, glycerol gelatin, and the like.

[0063] The present invention also provides a method for preventing or treating cachexia, which comprises administering to a patient the pharmaceutical composition for preventing or treating cachexia according to the present invention.

[0064] The therapeutic method of the present invention comprises administering a therapeutically effective amount of the pharmaceutical composition to an individual. The specific therapeutically effective amount for a particular individual will vary depending on various factors, including the type and degree of response to be achieved, the specific composition (including whether other preparations are used, if applicable), the individual's age, weight, general health, sex, and diet, the administration time, administration route, and excretion rate of the composition, the duration of treatment, and drugs used in conjunction with or concomitantly with the specific composition, as well as similar factors well known in the pharmaceutical field. Therefore, the effective amount of the composition suitable for the purpose of the present invention is preferably determined taking into account the above factors.

[0065] The patient can be any mammal, including humans and primates, as well as domestic animals such as cattle, pigs, sheep, horses, dogs and cats.

[0066] The method for preventing or treating cachexia of the present invention may be a method for simultaneously preventing or treating cancer-induced cachexia and cancer.

[0067] The present invention will be described in more detail with reference to the following examples, but the following examples are merely illustrative of the present invention and are not intended to limit the scope of the present invention.

[0068] Example 1: Preparation of a combined extract of Salvia miltiorrhiza and Rhubarb A complex extract of herbal medicine containing Salviae miltiorrhizae Radix and Rhei Radix et Rhizoma was prepared by mixing Salviae miltiorrhizae Radix and Rhei Radix at a weight ratio of 1:1 and extracting them with hot water. Specifically, after cleaning and washing the Salviae miltiorrhizae and Rhei Radix, 250 g of Salviae miltiorrhizae and 250 g of Rhei Radix were mixed and added to 1 L of distilled water, followed by boiling at 100°C for 2 hours to make a total volume of 500 ml. The decoction was freeze-dried to prepare a powdered Salviae miltiorrhizae and Rhei Radix Rhizoma complex extract (Example 1, DD).

[0069] In addition, 500 g of Salvia miltiorrhiza and 500 g of Rhubarb were used in the same manner as above to prepare a Salvia miltiorrhiza single extract and a Rhubarb single extract, respectively.

[0070] The yields of the Rhubarb and Salvia miltiorrhiza extracts were 20.80% and 31.72%, respectively. The extract powders were dissolved in triple distilled water and filtered through a 22 μm filter before use in the experiment.

[0071] <Experimental Example 1> Preparation of animal model To confirm the effect of the extract of the present invention on cancer cachexia, an obesity / cancer associated disease animal model was prepared.

[0072] Specifically, 7-week-old C57BL / 6J mice were fed a high-fat diet for five weeks. At week 5, C57BL / 6J-derived B16BL6 melanoma cells were injected subcutaneously into the left thigh of the mice to induce cancer (melanoma) and obesity. All groups were then fed a high-fat diet for an additional three weeks and administered the Danshen and Rhubarb complex extract (DD; orally administered three times a week) described in Example 1 or cisplatin (CIS; intraperitoneally administered once a week), an anticancer drug commonly used in melanoma treatment. The control group (high fat diet, HFD) and disease control group (HFD + B16BL6 injection) were fed a high-fat diet alone for three weeks after the induction of obesity or obesity / cancer, respectively, without any injections.

[0073] <Experimental Example 2> Effect of the complex extract on weight loss caused by cancer cachexia To confirm the induction of cancer cachexia and the ameliorating effects of the complex extract, body weight changes in mice were measured over a total of 8 weeks of treatment, as described in Example 1. To correct for differences in body weight due to cancer tissue, the weight of the tumor tissue was compared with the cancer-free body weight (the total body weight of the mice minus the weight of the tumor tissue) after 8 weeks of treatment. Weight changes in white adipose tissue (inguinal white adipose tissue, iWAT) and visceral abdominal fat (epididymal white adipose tissue, eWAT) were also measured. The results are shown in Figure 1.

[0074] As a result, as shown in Figure 1, in the non-cancer control group (HFD), body weight and white adipose tissue weight increased due to the ingestion of a high-fat diet, while in the obesity / cancer-induced disease control group (HFD + B16BL6 injection), a relative decrease in total body weight was observed. In particular, the weight of body weight and white adipose tissue excluding cancer tissue was significantly reduced compared to the control group, confirming the induction of cancer cachexia.

[0075] Meanwhile, in an obesity / cancer animal model, treatment with the composite extract (DD) of Example 1 significantly (p<0.05) reduced tumor weight compared to the disease control group, and this reduction showed an efficacy similar to that of the anticancer drug cisplatin (CIS) (Figure 1B).

[0076] In addition, in an obesity / cancer animal model, tumor-free body weight (TBAW) measured in the animal model treated with the composite extract (DD) of Example 1 was similar to that of the disease control group (HFD + B16BL6 injection), but treatment with the anticancer drug cisplatin (CIS) significantly reduced the weight (p<0.05) compared to the disease control group (Figure 1C). In particular, in the case of abdominal visceral fat (eWAT), treatment with the composite extract (DD) of Example 1 significantly inhibited the loss of fat due to cancer tissue compared to the disease control group (HFD + B16BL6 injection), maintaining a weight similar to that of the control group (HFD) (Figure 1E).

[0077] As a result, it was confirmed that the anticancer drug cisplatin can suppress the growth of cancer tissue, but cannot suppress weight loss and fat loss caused by cancer tissue, and in fact worsens the condition. On the other hand, the composite extract (DD) of Example 1 of the present invention exhibits an anticancer effect similar to that of cisplatin, while significantly suppressing weight loss and fat loss caused by cancer tissue, thereby exhibiting an excellent inhibitory effect on cancer cachexia.

[0078] <Experimental Example 3> Effect of the complex extract on the expression of cancer cell death indicator factors To measure the effect of the composite extract (DD) of Example 1 of the present invention on the expression of apoptosis factors in the cancer tissues of the animal model, changes in the expression levels of Bcl-xl and Bax, which are representative of the Bcl-family, which are mitochondrial inner and outer membrane proteins, and of caspase 3, which is a major mechanism of apoptosis, were confirmed using Western blot.

[0079] In Experiments 1 and 2, cancer tissue cells from animal models treated with the composite extract (DD) or cisplatin (CIS) were lysed in RIPA buffer [50 mM Tris-HCl (pH 7.5), 0.1% sodium dodecyl sulfate (SDS), 0.1% Triton X-100, 1% Nonidet P-40, 0.5% sodium deoxycholate, 150 mM NaCl, and 1 mM phenylmethylsulphonyl fluoride], separated by 8% sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and transferred to a nitrocellulose membrane. The membrane was blocked with 5% nonfat milk in TBST (10 mM Tris, 150 mM NaCl, and 0.05% Tween 20, pH 7.6) for 1 hour at room temperature. After washing with TBST, it was incubated overnight at 4°C with primary antibodies against Bax, Bcl-xL, caspase 3 (Thermo Scientific, Waltham, MA, USA), or actin (β-actin, Santa Cruz Biotechnology, Inc.). The membrane was then incubated with the appropriate horseradish peroxidase-conjugated secondary antibody (Amersham Biosciences, Westborough, MA, USA) for 2 hours at room temperature. Protein bands were detected using enhanced chemiluminescence (ECL) solution (Amersham Biosciences, Piscataway, NJ) with the LAS Image Gauge program according to the manufacturer's instructions. The results are shown in Figure 2.

[0080] As a result, as shown in Figure 2, the ratio of Bax / Bcl-xL increased in the combined extract (DD) treatment group compared to the disease control group, and in particular, the ratio of cleaved / pro-caspase 3 significantly increased, confirming the cancer-suppressing effect of caspase cascade activation.

[0081] The present invention has been described above with a focus on its preferred embodiments. Those skilled in the art will understand that the present invention can be embodied in various modified forms without departing from the essential characteristics of the present invention. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the present invention is defined by the appended claims, not the foregoing description, and all variations within the scope of the claims should be interpreted as being within the scope of the present invention.

Claims

1. A method for producing a pharmaceutical composition for preventing or treating cancer cachexia, which inhibits weight loss and fat loss induced by cancer, comprising the steps of mixing Danshen (Salviae Miltiorrhizae Radix) and Rhubarb (Rhei Radix et Rhizoma) and then extracting the mixture with hot water to produce a combined extract of Danshen and Rhubarb.

2. 2. The method of claim 1, wherein the weight ratio of Salvia miltiorrhiza and Rhubarb is 1:3 to 3:

1.

3. The method of claim 1, wherein the composition improves 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. The method of claim 3, wherein the composition improves one or more symptoms selected from the group consisting of weight loss and fat loss.

5. The method according to claim 1, wherein the composition simultaneously exhibits anti-cancer effects and anti-cancer cachexia effects.

6. The method according to claim 5 , wherein the anti-cancer effect is exhibited through activation of one or more factors selected from the group consisting of Bax and caspase 3.

7. A method for producing a health functional food composition for preventing or improving cancer cachexia, which inhibits cancer-induced weight loss and fat loss, comprising the steps of mixing Salvia miltiorrhiza and Rhubarb and then extracting them with hot water to produce a combined extract of Salvia miltiorrhiza and Rhubarb.

8. A method for producing a health food composition for preventing or ameliorating cancer-related cachexia, which inhibits cancer-induced weight loss and fat loss, comprising the steps of: mixing Salvia miltiorrhiza and Rhubarb in a weight ratio of 1:3 to 3:1; and then extracting the mixture with hot water to produce a combined extract of Salvia miltiorrhiza and Rhubarb.

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