JP2023548411A - A composition for preventing or treating cachexia containing a complex extract of Danjin and Rhubarb - Google Patents

Abstract

The present invention relates to a composition for preventing, improving or treating cachexia containing a complex extract of Danjin and Rhubarb, wherein the complex extract suppresses weight loss and fat loss due to cancer and induces cancer cell death. Therefore, it may be useful as a composition for preventing, ameliorating, or treating cancer cachexia, which can simultaneously perform anticancer treatment and improve cachexia without causing side effects of cachexia. [Selection diagram] Figure 1

Description

The present invention relates to a composition for preventing, ameliorating or treating cachexia containing a composite extract of Chinese herbal medicine, and more particularly to a composition for preventing, improving or treating cachexia containing a composite extract of Chinese herbal medicine (Salviae Miltiorrhizae Radix) and rhubarb (Rhei Radix et Rhizoma). The present invention relates to pharmaceutical compositions for preventing, improving or treating fluid quality, functional health food compositions, and anti-cancer adjuvant compositions.

Cachexia refers to a complex syndrome in which persistent muscle loss occurs due to various diseases such as cancer, heart failure, chronic obstructive pulmonary disease, chronic kidney disease, and acquired immune deficiency syndrome. Among these, cancer cachexia is a complex metabolic syndrome associated with malignant tumors, and is defined as a loss of body weight of 5% or more due to loss of muscle and fat within 6 months after the onset of cancer. . Cachexia can occur in a variety of medical conditions, and cancer cachexia has a close relationship with terminal cancer. Approximately 50% of all cancer patients, particularly approximately 80% of terminally ill cancer patients, are affected by cancer cachexia and suffer from reduced quality of 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, distinct from muscle and fat loss through appetite suppression.

Treatment agents for cancer cachexia include NSAIDs (non-steroidal anti-inflammatory drugs), β2-adrenergic agonists, corticosteroids, and ghrelin, which are currently the most commonly used drugs on the market to treat cancer cachexia. Been The drugs include COX-2 inhibitors and TNF-α inhibitors.

COX-2 inhibitors are drugs that reduce skeletal muscle loss by suppressing COX-2, which is involved in the production of prostaglandins, which are inflammatory substances that occur in large amounts in cancer tissues. Celecoxib is commercially available as a COX-2 inhibitor. However, celecoxib has been reported to have side effects such as anemia, gastric ulcer, allergy, heart attack, and stroke.

A TNF-α inhibitor is a drug that kills cancer cells by decreasing the expression of TNF-α, which is abundantly expressed in the serum of patients with cancer cachexia. Thalidomide is commercially available as a TNF-α inhibitor. However, these drugs are less effective as therapeutic agents for cancer cachexia, and have side effects such as depression, heart failure, dyspnea, vomiting, rash, high blood pressure, and birth of deformed babies during pregnancy.

As described above, most of the drugs currently under development or on the market have many side effects and lack evidence for their therapeutic effects. Therefore, there is an urgent need to develop therapeutic agents for cancer cachexia with a new mechanism.

On the other hand, Salviae Miltiorrhizae Radix is a Chinese herbal medicine derived from the root of Salvia miltiorrhiza Bunge, which belongs to the Lamiaceae family. It has been shown to have activity in inhibiting bone damage, osteoporosis, central nervous system action, anti-inflammatory, antioxidant, and anti-cancer actions.

Rhei Radix et Rhizoma is a perennial herb belonging to the Polygonaceae family.Rheum palmatum Linne, Rheum tanguticum Maximowicz ex Balf.) or medicinal rhubarb (Rheum officinale Baillon) root and It is a rhizome with the epidermis removed, and is clinically used to treat indigestion, constipation, acute inflammation, infectious diseases, parasitic diseases, bleeding, thrombocytopenia, burns, and skin diseases.

The present inventors have demonstrated that a complex extract of the natural products Danjin and Rhubarb inhibits cancer-induced weight loss and fat loss, induces cancer cell death, and exhibits significant anti-cancer effects in an obesity/cancer-associated disease animal model. The present invention was completed after confirming that it has an effect on improving cancer and cancer cachexia.

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

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

Another object of the present invention is to provide an anti-cancer adjuvant composition comprising the above pharmaceutical composition.

Another object of the present invention is to provide a method for preventing or treating cachexia.

To achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating cachexia, comprising a composite extract of Salviae Miltiorrhizae Radix and Rhei Radix et Rhizoma.

In one embodiment of the invention, the cachexia may be induced by cancer.

The present invention also provides a functional health food composition and a health food composition for preventing or improving cachexia, which contain a complex extract of Danjin and rhubarb.

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

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.

The complex extract of Danjin and Rhubarb of the present invention suppresses cancer-induced weight loss and fat loss in animal models of obesity/cancer-related diseases, and induces cancer cell death through caspase cascade activation, thereby exhibiting significant anti-inflammatory effects. Since it shows the effect of improving cancer and cancer cachexia, it can be useful as a composition for preventing, improving or treating cancer cachexia, which can simultaneously perform anti-cancer treatment and improve cachexia without cachexia side effects.

Body weight change, tumor weight of cancer tissue, and weight of cancer tissue excluded from the weight of all mice in an animal model of obesity/cancer-associated disease due to treatment with the complex extract of Danjin and rhubarb of the present invention This table shows the results of measuring changes in cancer free body weight, subcutaneous fat (internal white adipose tissue, iWAT), and abdominal visceral fat (eWAT). It is. This figure shows the effect of a combined extract of Danjin and Rhubarb on the expression of cancer cell killing-related factors (Bcl-xl, Bax, cleaved-caspase 3, and caspase 3).

The present invention will be explained in detail below.

Pharmaceutical composition for the prevention or treatment of cachexia The present invention provides a pharmaceutical composition for the prevention or treatment of cachexia containing a complex extract of Salviae Miltiorrhizae Radix and Rhei Radix et Rhizoma. compositions.

The term "cachexia" used herein refers to severe systemic debilitating symptoms seen in the terminal stages of cancer, tuberculosis, diabetes, acquired immunodeficiency syndrome (AIDS), etc. It often appears in patients with gastrointestinal cancers such as stomach cancer, esophageal cancer, pancreatic cancer, and colon cancer, as well as in patients with lung cancer. Symptoms include loss of appetite, loss of body weight and physical strength due to loss of muscle and fat, anemia, lethargy, and indigestion. In particular, it refers to a condition in which weight decreases even when eating and drinking normally. Once cachexia develops, it shows a poor response to anti-cancer chemotherapy and radiation therapy, resulting in a poor quality of life for patients, shortening their life expectancy, and affecting 10 to 20% of all cancer patients. Induces death due to reduction.

In the pharmaceutical composition according to the present invention, the cachexia may be induced by cancer. In one embodiment of the present invention, the cancer-induced cachexia is expressed as "cancer cachexia".

Cancers defined in this application 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, and hepatocellular carcinoma. 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, digestion May include ductal stromal tumors (GIST), cancers of unknown origin, mesothelioma, neuroendocrine tumors, skin cancers, blood cancers, and the like.

The pharmaceutical composition according to the present invention 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. It may well and preferably improve one or more symptoms selected from the group consisting of weight loss and fat loss.

The pharmaceutical composition according to the present invention may exhibit anticancer effects and cancer cachexia suppressing effects at the same time.

The anticancer effect may be exhibited through activation of one or more factors selected from the group consisting of Bax and caspase 3. Preferably, it may exhibit a cancer cell killing effect through caspase cascade activation.

According to one embodiment of the present invention, a complex extract of Danjin and Rhubarb shows the effect of improving weight loss and fat loss caused by cancer tissue in an obesity/cancer-associated disease animal model, and Bax acts as a factor for killing cancer cells. By showing the effect of activating the expression of caspase3 and the effect of suppressing cancer, it was confirmed that the anticancer effect and the effect of improving cancer cachexia were confirmed (see Experimental Examples 1 to 3).

The above-mentioned effects may be such that the combined extract of Danjin and rhubarb of the present invention has a significantly increased effect compared to each individual extract.

In the present invention, the composite extract of Rhubarb and Rhubarb may be an extract of a mixture of Rhubarb and Rhubarb, or may be a mixture of extracts obtained by extracting each of Rhubarb and Rhubarb. There are no restrictions on

The above-mentioned "extract" refers to a preparation obtained by squeezing out the extraction target with an appropriate exudate and evaporating the exudate to concentrate, and includes, but is not limited to, an extract obtained by extraction processing, It may be a diluted or concentrated solution of the extract, a dried product obtained by drying the extract, or a crudely purified product or purified product thereof. The extraction method is not limited thereto, but preferably hot water extraction, hot water extraction, cold immersion extraction, reflux cooling extraction, or ultrasonic extraction can be used.

For example, the composite extract is produced by a method comprising: mixing Danjin and rhubarb; and soaking the mixture in water, C1 to C4 alcohol, ethyl acetate, or a mixture thereof to obtain an extract. However, there is no limitation to this. At this time, the C1 to C4 alcohol may be ethanol, methanol, butanol, or a combination thereof. Extraction may be carried out by adding the extraction solvent in an amount of 1 to 10 times the weight of the mixture of Danjin and rhubarb. The extraction temperature may be from 30 to 120°C, but is not limited thereto. Further, the extraction time may be from 2 to 48 hours, but is not limited thereto.

The tanjin 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, they may be mixed at a weight ratio of 1:3 to 3:1, and most preferably, they may be mixed at a weight ratio of 1:2 to 2:1. .

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 invention may be formulated for oral, intramuscular, intravenous, intraperitoneal, subcutaneous, intradermal, or topical administration. It's fine.

The complex extract of Danjin and Rhubarb of the present invention may be administered in various oral and parenteral dosage forms during clinical administration, and when formulated, it may be prepared using commonly used fillers, extenders, binders, and wetting agents. , disintegrants, surfactants, and other diluents or excipients.

Solid formulations for oral administration include tablets, pills, powders, granules, capsules, lozenges, etc., and such solid formulations include one or more of the combined extracts of Danjin and Rhubarb of the present invention. It is prepared by mixing the product with at least one or more excipients, such as starch, calcium carbonate, sucrose, lactose, or gelatin. In addition to mere excipients, lubricants such as magnesium stearate talc are also used. Liquid preparations for oral administration include suspensions, internal solutions, emulsions, syrups, etc. In addition to commonly used diluents such as water and liquid paraffin, various excipients, such as humectants, may be used. agents, sweeteners, flavoring agents, preservatives, and the like.

Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations, suppositories, and the like. As non-aqueous solvents and suspending agents, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, etc. may be used. As a base for suppositories, witepsol, macrogol, tween 61, cocoa butter, lauric butter, glycerol, gelatin, etc. may be used.

The pharmaceutical composition may further include a carrier, excipient or diluent. The carrier, excipient, or diluent can be, for example, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, It may include crystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoic acid, propylhydroxybenzoic acid, talc, magnesium stearate, or mineral oil.

In addition, the pharmaceutical composition may further include known active ingredients having cancer cachexia preventive or therapeutic activity.

The effective dosage for humans of the complex extract of Danjin and Rhubarb of the present invention may vary depending on the patient's age, weight, sex, mode of administration, health condition, and degree of disease, and is generally about 0.001 -100 mg/kg/day, preferably 0.01-35 mg/kg/day. Based on an adult patient weighing 70 kg, the dose is generally 0.07 to 7000 mg/day, preferably 0.7 to 2500 mg/day, and administered at regular intervals depending on the judgment of a doctor or pharmacist. It may be administered in divided doses from once a day to several times a day.

Healthy functional food and health food composition for preventing or improving cachexia The present invention also provides a functional health food and health food composition for preventing or improving cachexia. ) To provide a health functional food composition for prevention or improvement.

Further, the present invention provides a health food composition for preventing or improving cachexia, which includes a composite extract of Salviae Miltiorrhizae Radix and Rhei Radix et Rhizoma.

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

The functional health food composition or health food composition according to the present invention 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. Preferably, it may improve one or more symptoms selected from the group consisting of weight loss and fat loss.

The functional health food composition or health food composition according to the present invention may exhibit anticancer effects and cancer cachexia suppressing effects at the same time.

The anticancer effect may be exhibited through activation of one or more factors selected from the group consisting of Bax and caspase 3. Preferably, it may exhibit a cancer cell killing effect through caspase cascade activation.

According to one embodiment of the present invention, a complex extract of Danjin and Rhubarb shows the effect of improving weight loss and fat loss caused by cancer tissue in an obesity/cancer-associated disease animal model, and Bax acts as a factor for killing cancer cells. By showing the effect of activating the expression of caspase3 and the effect of suppressing cancer, it was confirmed that the anticancer effect and the effect of improving cancer cachexia were confirmed (see Experimental Examples 1 to 3).

The term "healthy functional food" used in the present invention refers to foods manufactured and processed in the form of tablets, capsules, pills, liquids, powders, and granules using raw materials and ingredients that have functionality useful for the human body. Say food. Here, "functionality" means adjusting nutrients to the structure and function of the human body, or obtaining effects useful for health applications such as physiological effects. The functional health food of the present invention can be manufactured by a method commonly used in the ordinary technical field, and can be manufactured by adding raw materials and components that are usually added in the ordinary technical field. Further, the dosage form of the health functional food can be manufactured without any restriction as long as it is a dosage form that is recognized as a health functional food. The functional health food composition of the present invention can be manufactured in various dosage forms, and unlike general drugs, it has the advantage that it is made from food and does not have side effects that can occur when taking drugs for a long period of time. The functional health food of the present invention is highly portable and can be taken as an adjunct to enhance the effects of cancer cachexia treatment agents or anticancer agents.

The health functional food composition or health food composition according to the present invention is a health functional food such as a food, a drink, or a health food containing the complex extract of Danjin and rhubarb for the purpose of preventing or improving cancer cachexia. can be added to.

There are no particular restrictions on the type of food. Examples of foods to which the complex extract of Danjin and Rhubarb according to the present invention can be added include drinks, meats, sausages, bread, biscuits, rice cakes, chocolates, candies, snacks, sweets, pizza, and ramen noodles. , other noodles, gums, dairy products including ice creams, various soups, drinking water, alcoholic beverages and vitamin complexes, dairy products and dairy processed products, etc., and are health foods and health functional foods in the usual sense. Including all.

The health functional foods and health food compositions according to the present invention may be added to foods as they are, or may be used together with other foods or food ingredients, and may be used appropriately by conventional methods. The mixing amount of the complex extract of Danjin and Rhubarb according to the present invention can be suitably determined depending on the intended use (preventive or ameliorative). Generally, the amount of the complex extract of Danjin and rhubarb in health foods and health functional foods may be 0.1 to 90 parts by weight based on the total weight of the food. However, in the case of long-term intake for the purpose of maintaining health or regulating health, the above-mentioned amount may be less than the above-mentioned range, and there is no problem in terms of safety, so it is effective. Amounts above the above ranges can also be used.

The health food and health functional food compositions of the present invention contain the complex extracts of Danjin and Rhubarb according to the present invention as essential ingredients in the indicated proportions, and there are no special restrictions on other ingredients. As with beverages, they may contain additional ingredients such as various flavoring agents or natural carbohydrates. Examples of natural carbohydrates mentioned above are monosaccharides, e.g. glucose, fructose, etc.; disaccharides, e.g. maltose, sucrose, etc.; and polysaccharides, e.g. common sugars such as dextrins, cyclodextrins, etc., and xylitol, sorbitol, Sugar alcohols such as erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (thaumatin, stevia extract (e.g. rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can advantageously be used.The proportion of said 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.

In addition to the above, the health food and health functional food compositions containing the complex extract of Danjin and rhubarb according to the present invention may also contain various nutritional supplements, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, Colorants and fillers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohol, carbonated drinks. It may contain a carbonating agent used in In addition, the health food and health functional food compositions of the present invention may include natural fruit juice and fruit pulp for the production of fruit juice drinks and vegetable drinks.

Such components can be used independently or in combination. The proportion of such additives is not limited to this, but may be selected in the range of 0.1 to about 20 parts by weight per 100 parts by weight of the health food and functional health food composition containing the active substance of the present invention. Common.

Anticancer adjuvant composition The present invention also provides an anticancer adjuvant composition comprising the pharmaceutical composition for preventing or treating cachexia according to the present invention.

The term "anticancer adjuvant" used in the present invention can be used to increase the anticancer treatment effect, suppress or improve the side effects of anticancer drugs, and can be administered to patients in combination with anticancer drugs. can be done.

The anticancer adjuvant composition of the present invention exhibits the effect of suppressing or improving cachexia symptoms such as muscle loss, weight loss, fat loss, hematopoietic toxicity, and appetite loss induced by cancer, It may increase the cancer effect.

Existing anticancer drugs defined in this application include cisplatin, cyclophosphamide, methotrexate, 5-fluorouracil, doxorubicin, mustin ne), vincristine, procarbazine, prednisolone, bleomycin, vinblastine, dacarbazine, etoposide, epirubicin cin), cisplatin, capecitabine, oxaliplatin It may include the following.

The anti-cancer adjuvant composition may further contain one or more active ingredients that exhibit the same or similar functions, in addition to the combined extract of Danjin and Rhubarb as active ingredients. The anticancer adjuvant can be administered orally or parenterally during clinical administration, and when administered parenterally, it can be administered by intraperitoneal injection, intrarectal injection, subcutaneous injection, intravenous injection, intramuscular injection, endometrial injection, or cerebrovascular injection. It may be administered by intra- or intrathoracic injection and may be used in the form of common pharmaceutical formulations.

The anti-cancer therapies may be used alone or in combination with surgery, radiation therapy, hormonal therapy, chemotherapy and methods using biological response modifiers. The daily dosage of the anticancer adjuvant is about 0.0001 to 1000 mg/kg, preferably 1 to 100 mg/kg, and is preferably administered once to several times a day. The range varies depending on the patient's weight, age, sex, health condition, diet, administration time, administration method, excretion rate, severity of disease, etc. The anticancer adjuvant of the present invention may actually be administered in various parenteral dosage forms during clinical administration, but when formulated into a formulation, it is necessary to use commonly used fillers, extenders, binders, wetting agents, disintegrators, etc. It is formulated using diluents or excipients such as peptizers and surfactants. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations, and suppositories. As non-aqueous solvents and suspending agents, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, etc. may be used. As a base for suppositories, witepsol, macrogol, tween 61, cocoa butter, lauric butter, glycerol gelatin, etc. may be used.

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.

The method of treatment of the present invention comprises administering the pharmaceutical composition to an individual in a therapeutically effective amount. The specific therapeutically effective amount for a particular individual will depend on the type and extent of the response sought to be achieved, the specific composition, including if any other formulations are used, the age, weight, and age of the individual; A variety of factors including general health, gender and diet, time of administration, route of administration and secretion rate of the composition, duration of treatment, specific composition and drugs used with or concomitantly with the pharmaceutical field. It is preferred to apply differently by known similar factors. Therefore, the effective amount of the composition suitable for the purpose of the present invention is preferably determined in consideration of the above matters.

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

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

Hereinafter, the present invention will be explained in more detail with reference to the following examples. However, the following examples merely illustrate the present invention, and the content of the present invention is not limited to the following examples.

<Example 1> Production of composite extract of Salviae miltiorrhizae and Rhizoma A Chinese herbal medicine composite extract containing Salviae miltiorrhizae Radix and Rhei Radix et Rhizoma was prepared by mixing Salviae miltiorrhizae and Rhizoma in a weight ratio of 1:1. Produced by hot water extraction. Specifically, after cleaning and cleaning the Dangjin and rhubarb chemicals, 250 g of Dangjin and 250 g of Rheum were mixed, added to 1 L of distilled water, and boiled at 100° C. for 2 hours to make a total volume of 500 ml. The decoction liquid was freeze-dried to produce a powdered Danjin and Rhubarb complex extract (Example 1, DD).

Further, a single extract of Dansin and a single extract of Rhubarb were prepared using 500 g of Dansin and 500 g of Rhubarb using the same method as described above.

At this time, the yields of the rhubarb and tanjin extracts were 20.80% and 31.72%, respectively. Each of the extract powders was dissolved in tertiary distilled water, filtered through a 22 μm filter, and used in the experiment.

<Experimental Example 1> Preparation of Animal Model In order to confirm the effect of the extract of the present invention on cancer cachexia, an obesity/cancer-associated disease animal model was prepared.

Specifically, 7-week-old C57bl/6j mice were fed a high-fat diet for 5 weeks, and at the 5th week, B16BL6 cells, which are C57bl/6j-derived melanoma cells, were subcutaneously injected into the left thigh of the mice to induce cancer. (melanoma) and induced obesity. After this, all groups were fed a high-fat diet for an additional three weeks and treated with either the Danjin and rhubarb complex extract (DD; oral administration, three times a week) of Example 1 or an anticancer drug often used in melanoma treatment. A certain cisplatin (CIS; intraperitoneal administration, once a week) was administered. A control group (high fat diet, HFD) and a disease control group (HFD+B16BL6 injection) were fed only high fat diet without any injection for 3 weeks after obesity or obesity/cancer induction, respectively.

<Experimental Example 2> Effect of the composite extract on improving weight loss due to cancer cachexia In order to confirm the induction of cancer cachexia and the improving effect of the composite extract, an experiment was conducted for a total of 8 weeks using the same method as in Example 1 above. The body weight change of the mice was measured during the treatment period. In addition, in order to correct for differences in body weight due to cancer tissue, after a total of 8 weeks of treatment, the weight of cancer tissue (tumor weight) and the weight of all mice minus the weight of cancer tissue (cancer free body weight) were calculated. We also measured changes in the weight of subcutaneous fat (inguinal white adipose tissue, iWAT) and abdominal visceral fat (eWAT), which are white adipose tissue. The measurement results for each weight are as shown in FIG.

As a result, as shown in Figure 1, in the control group (HFD) in which cancer was not induced, body weight and white adipose tissue weight increased due to high-fat diet intake, while obesity/cancer-induced disease increased. In the control group (HFD + B16BL6 injection), it was observed that the total body weight was relatively reduced, and in particular, the weight excluding cancer tissue and the weight of white adipose tissue were significantly reduced compared to the control group. It was confirmed that cancer cachexia was induced.

On the other hand, in an obesity/cancer-associated disease animal model, when treated with the composite extract (DD) of Example 1, the tumor weight of cancer tissue was significantly reduced (p<0.05) compared to the disease control group. This reduction was shown to have a similar level of efficacy to the anticancer drug cisplatin (CIS) (FIG. 1B).

Furthermore, the tumor free body weight of the obesity/cancer-associated disease animal model treated with the composite extract (DD) of Example 1 was similar to that of the disease control group (HFD+B16BL6 injection). However, when treated with the anticancer drug cisplatin (CIS), it was significantly (p<0.05) reduced compared to the disease control group (Figure 1C). In particular, in the case of abdominal visceral fat (eWAT), when treated with the composite extract (DD) of Example 1, fat loss caused by cancer tissue was significantly suppressed compared to the disease control group (HFD+B16BL6 injection), and ), it was confirmed that it was possible to maintain a weight almost similar to that of (Fig. 1E).

As a result, although cisplatin, an anticancer drug, can suppress the increase in cancer tissue, it cannot suppress the weight loss and fat loss caused by cancer tissue, and on the contrary, the compound of Example 1 of the present invention Extract (DD) has been shown to have an anticancer effect similar to that of cisplatin, while also significantly inhibiting weight loss and fat loss caused by cancer tissue, thereby exhibiting an excellent inhibitory effect on cancer cachexia. confirmed.

<Experimental Example 3> Effect of the composite extract on the expression of cancer cell death indicator factors The effect of the composite extract (DD) of Example 1 of the present invention on the expression of cell death (apoptosis) factors was measured in the cancer tissue of the above animal model. In order to do this, we investigated the expression levels of Bcl-xl and Bax, which are representative mitochondrial inner and outer membrane proteins of the Bcl-family, and the expression level of caspase 3, which is a representative caspase cascade, which is a major mechanism of cell death. Changes were confirmed using Western blot.

In Experimental Examples 1 and 2, animal model cancer tissue cells treated with complex extract (DD) or cisplatin (CIS) were treated with RIPA buffer [50 mM Tris-HCl (pH 7.5), 0.1% dodecyl]. Sodium dodecyl sulfate (SDS), 0.1% Triton enylmethylsulfonyl fluoride], separated by 8% sodium dodecyl sulfate polyacrylamide gel electrophoresis, and transferred to a nitrocellulose membrane. The membrane was blocked with TBST (10mM Tris, 150mM NaCl and 0.05% Tween20, pH 7.6) containing 5% skim milk for 1 hour at room temperature, washed with TBST, and then treated with Bax, Bcl- xL, Caspase 3 (Thermo Scientific, Waltham, MA, USA) or actin (β-actin, Santa Cruz Biotechnology, Inc.) primary antibodies were incubated overnight at 4°C. The membranes were then reacted with secondary antibodies (Amersham Biosciences, Westborough, MA, USA) attached with the appropriate horseradish peroxidase (Jackson Lab.) for 2 hours at room temperature. Protein bands of interest were measured in the LAS Image Gauge program using enhanced chemiluminescence (ECL) solution (Amersham Bioscience, Piscataway, NJ) according to the manufacturer's instructions, and the results were analyzed using the LAS Image Gauge program. It is shown in Figure 2.

As a result, as shown in Figure 2, the ratio of Bax/Bcl-xL increased in the complex extract (DD) treated group compared to the disease control group, and in particular, the ratio of cleaved/pro caspase 3 significantly increased. From this perspective, it was confirmed that there is a cancer suppressing effect due to caspase cascade activation.

Up to now, the present invention has been discussed mainly on its preferred embodiments. Those skilled in the art to which the present invention pertains should be able to understand that the present invention can be embodied in modified forms without departing from the essential characteristics of the present invention. As such, the disclosed embodiments should be considered in an illustrative rather than a restrictive light. The scope of the invention is indicated in the claims rather than in the foregoing description, and all differences within the scope of equivalency are to be construed as included in the invention.

Claims (12)

A pharmaceutical composition for preventing or treating cachexia, comprising a complex extract of Salviae Miltiorrhizae Radix and Rhei Radix et Rhizoma. 2. The pharmaceutical composition according to claim 1, wherein the cachexia is induced by cancer. 2. 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. Pharmaceutical composition of. 4. The pharmaceutical composition of claim 3, wherein the composition ameliorates one or more symptoms selected from the group consisting of weight loss and fat loss. The pharmaceutical composition according to claim 1, wherein the composition simultaneously exhibits an anticancer effect and an inhibitory effect on cancer cachexia. 6. The pharmaceutical composition according to claim 5, wherein the anticancer effect is exhibited through activation of one or more factors selected from the group consisting of Bax and caspase 3. A health functional food composition for preventing or improving cachexia, containing a complex extract of Danjin and rhubarb. The functional health food composition according to claim 7, wherein the cachexia is induced by cancer. A health food composition for preventing or improving cachexia, containing a complex extract of Danjin and rhubarb. The health food composition according to claim 9, wherein the cachexia is induced by cancer. An anticancer adjuvant composition comprising the pharmaceutical composition for preventing or treating cachexia according to claim 1. A method for preventing or treating cancer and cachexia, which comprises administering to a patient the pharmaceutical composition for preventing or treating cachexia according to claim 1.