KR102477343B1 - Composition for preventing or treating cachexia comprising medicinal herb complex extract - Google Patents

Abstract

The present invention relates to a composition for preventing, improving or treating cachexia comprising a composite extract of Cyperi Rhizoma and Zanthoxyli Pericarpium, wherein the composite extract of the present invention inhibits weight loss and fat loss caused by cancer and , By inducing cancer cell death, it exhibits significant cancer suppression and cancer cachexia inhibitory effects, so it can be useful as a composition for preventing, improving, or treating cancer cachexia, which can simultaneously treat anti-cancer treatment and improve cachexia without cachexia side effects.

Description

Composition for preventing or treating cachexia comprising medicinal herb complex extract}

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 a pharmaceutical composition, a health functional food composition, and an anti-cancer adjuvant composition.

Cachexia refers to a complex syndrome resulting in persistent muscle loss caused by various diseases, including cancer, heart failure, chronic obstructive pulmonary disease, chronic kidney disease, and AIDS. Among them, cancer cachexia is a complex metabolic syndrome accompanied by malignant tumors, and is defined as a weight loss of 5% or more due to muscle and fat loss within 6 months after cancer occurs. Cachexia can occur in various medical conditions, but cancerous cachexia has a close relationship with terminal cancer. About 50% of all cancer patients, especially about 80% of terminal cancer patients, are affected by cancer 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 marked loss of muscle mass and/or adipose tissue, and is distinct from muscle and fat loss through appetite suppression.

Treatments for cancer cachexia include NSAIDs (non-steroidal anti-inflammatory drugs), β2-adrenergic agonists, corticosteroids, and ghrelin. The drugs most commonly used to treat cancer cachexia that have been marketed so far are COX-2 inhibitors and TNF-2 inhibitors. There are α inhibitors.

A COX-2 inhibitor is a drug that reduces loss of skeletal muscle by inhibiting COX-2 involved in the production of prostaglandins, an inflammatory substance that is generated in large amounts in cancer tissues. As a COX-2 inhibitor, celecoxib is commercially available. However, side effects such as anemia, gastric ulcer, allergy, heart attack and stroke have been reported with celecoxib.

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

As such, most of the drugs currently being developed or marketed have many side effects, and evidence for their therapeutic effect is lacking. Therefore, there is an urgent need to develop a new mechanism of cancer cachexia treatment.

On the other hand, Cyperi Rhizoma is a rhizome of Cyperus rotundus Linne belonging to the family Cyperaceae, and is a herbal medicine that means the removal of thin roots. It is known to facilitate blood circulation, and is widely used for menstrual irregularities, dysmenorrhea, and gynecological diseases before and after childbirth as a pain reliever and blood purifying medicine. In addition, it is put in a prescription as a fever reducer and digestive medicine and is used for colds, headaches, abdominal pain, and loss of appetite.

Zanthoxyli Pericarpium (川椒) is the dried pericarp of the ripe fruit of the Zanthoxylum piperitum AP Dc. belonging to the Rutaceae family. In oriental medicine, it is said to be hot and has a fever, so it is used to remove cold energy by acting on the spleen, stomach, and kidneys, and is used to relieve pain.

The present inventors have found that the complex extracts of natural products Hyangbuja and Cheoncho suppress cancer-induced weight loss and fat loss in obesity/cancer comorbid animal models, induce cancer cell death, and have significant anticancer and cancer cachexia improvement effects. As confirmed, the present invention was completed.

Korean Patent Publication No. 10-2019-0103985

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 health functional food composition and health food composition for preventing or improving cachexia.

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

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

In order to achieve the above purpose,

The present invention provides a pharmaceutical composition for preventing or treating cachexia comprising a composite extract of Cyperi Rhizoma and Zanthoxyli Pericarpium.

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

In addition, the present invention provides a health functional food composition and a health food composition for preventing or improving cachexia comprising a composite extract of Hyangbuja and Cheoncho.

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 comprising administering the pharmaceutical composition for preventing or treating cachexia to a patient.

The composite extracts of Hyangbuja and Cheoncho of the present invention suppress cancer-induced weight loss and fat loss in animal models of obesity/cancer comorbidities, and induce cancer cell death, thereby exhibiting significant anticancer and cancer cachexia improvement effects, thereby reducing cachexia. It may be useful as a composition for preventing, improving, or treating cancerous cachexia, in which anticancer treatment and cachexia improvement are simultaneously possible without side effects.

Figure 1 shows the body weight change (body weight change) for 7 weeks of obesity / cancer comorbidity animal model according to the treatment of the composite extract of the present invention.
Figure 2 shows the body weight, cancer tissue weight, subcutaneous fat (inguinal white adipose tissue, iWAT) and abdomen of an animal model with obesity/cancer accompanying diseases according to the treatment of the composite extract of fragrant rich and cheoncho of the present invention. It shows the result of measuring the weight of epididymal white adipose tissue (eWAT).
Figure 3 shows the effect on the expression of cancer apoptosis-related factors (Bcl-xl, Bax, cleaved-caspase 3 and caspase 3) of the composite extract of Hyangbuja and Cheoncho.

Hereinafter, the present invention will be described in detail.

Pharmaceutical composition for preventing or treating cachexia

The present invention provides a pharmaceutical composition for preventing or treating cachexia comprising a composite extract of Cyperi Rhizoma and Zanthoxyli Pericarpium.

In the present invention, the Cyperi Rhizoma is a rhizome of Cyperus rotundus Linne belonging to the family Cyperaceae, from which thin roots are removed.

In the present invention, the cheoncho (Zanthoxyli Pericarpium, 川椒) is a dried pericarp of a ripe fruit of Zanthoxylum piperitum AP Dc. belonging to the Rutaceae (Rutaceae).

As used herein, the term 'cachexia' refers to a high level of systemic debilitating symptoms that can be seen in the terminal stages of cancer, tuberculosis, diabetes, acquired immunodeficiency syndrome (AIDS), and cancer of the stomach, esophagus, or pancreas. It is frequently seen in patients with digestive cancer, such as colorectal cancer, and lung cancer. It shows symptoms such as loss of appetite, loss of body weight and physical strength due to reduction of muscle and fat, anemia, lethargy, and indigestion, and in particular, indicates a state in which weight is reduced even if food is consumed normally. When cachexia occurs, patients show a low response to chemotherapy or radiation treatment, 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.

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

Cancer as defined herein is melanoma, leukemia, lymphoma, myeloma, myelodysplastic syndrome, breast cancer, head and neck cancer, esophageal cancer, stomach cancer, colon cancer (= colon cancer), rectal cancer, anal cancer, hepatocellular liver cancer, bile duct cancer, gallbladder cancer, pancreatic cancer, lung cancer (non-small cell lung cancer, small cell lung cancer), thymus cancer, kidney cancer, bladder cancer, prostate cancer, testicular cancer, ovarian cancer, cervical cancer, sarcoma, gastrointestinal stromal tumor (GIST, gist), cancer of unknown primary site, mesothelioma, It may include neuroendocrine tumors, skin cancer, blood cancer, and the like.

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 weight loss. and improving one or more symptoms selected from the group consisting of weight loss and fat loss.

The pharmaceutical composition according to the present invention may simultaneously exhibit anticancer effects and cancer cachexia inhibitory effects.

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

According to one embodiment of the present invention, the composite extracts of Hyangbuja and Cheoncho showed an effect of improving weight loss and fat loss by cancer tissue in obesity/cancer comorbid animal models, and Bax and By showing the effect of activating the expression of caspase3 and the effect of suppressing cancer, the effect of improving cancer cachexia at the same time as the anticancer effect was confirmed (see Experimental Examples 1 to 3).

The above effect may be that the effect of the composite extract of Hyangbuja and Cheoncho of the present invention is significantly increased compared to each single extract.

In the present invention, the composite extract of fragrant rich and cheoncho may be a mixture of fragrant rich and fragrant, and may be a mixture of single extracts obtained by extracting fragrant, rich and fragrant, respectively, but is not limited thereto.

The "extract" refers to a preparation obtained by squeezing an extraction target into an appropriate leachate and evaporating the leachate and concentrating the leachate, but is not limited thereto, but is not limited thereto. It may be a dried product obtained, a product prepared by these products, or a purified product. The extraction method is not limited thereto, but preferably, methods such as hot water extraction, hot water extraction, cold needle extraction, reflux cooling extraction, or ultrasonic extraction may be used.

For example, the complex extract is mixed with the fragrance rich 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 including, but is not limited thereto. In this case, the C1 to C4 alcohol may be ethanol, methanol, butanol, or a combination thereof. Extraction may be performed by adding the extraction solvent in an amount of 1 to 10 times the weight of the mixture of fragrant rich plants and cheoncho. The extraction temperature may be 30 to 120 ° C, but is not limited thereto. In addition, the extraction time may be 2 to 48 hours, but is not limited thereto.

The fragrant rich and cheoncho 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 1: 3 to 3: It may be to mix 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 into 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 composite extracts of fragrant rich and cheoncho of the present invention can be administered in various oral and parenteral formulations at the time of clinical administration, and when formulated, commonly used fillers, extenders, binders, wetting agents, disintegrants, diluents such as surfactants or prepared using excipients.

Solid preparations for oral administration include tablets, patients, powders, granules, capsules, troches, etc., and these solid preparations contain at least one excipient, for example, starch It is prepared by mixing calcium carbonate, sucrose, lactose or gelatin. In addition to simple excipients, lubricants such as magnesium styrate and talc are also used. Liquid formulations for oral administration include suspensions, internal solutions, emulsions, or syrups. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. can

Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspension solutions, emulsions, freeze-dried formulations, suppositories, and the like. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerol, gelatin, and the like may 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, alginates, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, or mineral oil.

In addition, the pharmaceutical composition may further include a known active ingredient having an activity for preventing or treating cancer cachexia.

An effective dose for the human body of the complex extract of fragrant rich and cheoncho of the present invention may vary depending on the patient's age, weight, sex, dosage form, health condition and disease degree, and is generally about 0.001 to 100 mg/kg/day. And, preferably 0.01 ~ 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 or twice a day at regular intervals according to the judgment of a doctor or pharmacist. It may be divided into several doses.

Health functional food and health food composition for preventing or improving cachexia

In addition, the present invention provides a health functional food composition for preventing or improving cachexia comprising a composite extract of Cyperi Rhizoma and Zanthoxyli Pericarpium.

Furthermore, the present invention provides a health food composition for preventing or improving cachexia comprising a composite extract of Cyperi Rhizoma and Zanthoxyli Pericarpium.

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

The health functional food composition or health food composition according to the present invention may improve at least one symptom selected from the group consisting of decreased appetite, weight loss, increased fatigue, increased inflammation, muscle loss, fat loss, and hematopoietic toxicity, Preferably, one or more symptoms selected from the group consisting of weight loss and fat loss may be improved.

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

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

According to one embodiment of the present invention, the composite extracts of Hyangbuja and Cheoncho showed an effect of improving weight loss and fat loss by cancer tissue in obesity/cancer comorbid animal models, and Bax and By showing the effect of activating the expression of caspase3 and the effect of suppressing cancer, the effect of improving cancer cachexia at the same time as the anticancer effect was confirmed (see Experimental Examples 1 to 3).

The term "health functional food" used in the present invention refers to food prepared and processed in the form of tablets, capsules, pills, liquids, powders and granules using raw materials or ingredients having useful functionalities for the human body. Here, 'functionality' means obtaining useful effects for health purposes, such as adjusting nutrients for the structure and function of the human body or physiological functions. The health functional food of the present invention can be manufactured by a method commonly used in the conventional technical field, and can be prepared by adding raw materials and components commonly added in the conventional technical field at the time of manufacture. In addition, the formulation of the health functional food may also be manufactured without limitation as long as the formulation is recognized as a health functional food. The health functional food composition of the present invention can be prepared in various types of formulations, and unlike general drugs, it has the advantage of using food as a raw material and free from side effects that can occur when taking drugs for a long time, and has excellent portability. The health functional food of the present invention can be consumed as an adjuvant to enhance the effectiveness of cancer cachexia treatment or anticancer drug.

The health functional food composition or health food composition according to the present invention can be added to health functional food or health food such as food, beverage, etc. for the purpose of preventing or improving cancerous cachexia.

There is no particular limitation on the type of food. Examples of foods to which the complex extracts of fragrant rich and cheoncho according to the present invention can be added are drinks, meat, sausages, bread, biscuits, rice cakes, chocolates, candies, snacks, confectionery, pizza, ramen, other noodles, gums, and 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 foods or food ingredients, and may be appropriately used according to conventional methods. The mixing amount of the composite extract of fragrant rich and cheoncho according to the present invention may be suitably determined according to its purpose of use (for prevention or improvement). In general, the amount of the complex extract of the herb rich and cheoncho in the health food and health functional food may be added in an amount of 0.1 to 90 parts by weight of the total weight of the food. However, in the case of long-term intake for the purpose of health maintenance or health control, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount greater than the above range.

The health food and health functional food composition of the present invention is not particularly limited in other ingredients, except for containing the complex extracts of jade rich and cheoncho according to the present invention as essential ingredients in the indicated ratio, and various flavors or natural ingredients like conventional beverages. Carbohydrates and the like may be contained as additional components. Examples of the aforementioned 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 dextrins, cyclodextrins, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (thaumatin, stevia extract (eg rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can advantageously be used. The ratio of the natural carbohydrate 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 composition containing the complex extracts of fragrant rich and cheoncho according to the present invention are various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and enhancers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. . In addition, the health food and health functional food composition of the present invention may contain fruit flesh for preparing natural fruit juice, fruit juice beverages, and vegetable beverages.

These components may be used independently or in combination. The ratio of these additives is not limited thereto, but is generally selected in 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.

Anticancer adjuvant composition

In addition, the present invention provides an anti-cancer adjuvant composition comprising the pharmaceutical composition for preventing or treating cachexia according to the present invention.

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

The anticancer adjuvant composition of the present invention exhibits an effect of suppressing or improving cachexia symptoms such as muscle loss, weight loss, fat loss, hematopoiesis, and appetite loss caused by cancer, thereby increasing the anticancer effect of the anticancer agent. .

Existing anticancer drugs defined herein include cisplatin, cyclophosphamide, methotrexate, 5-fluorouracil, doxorubicin, mustine, bicristine ( vincristine, procarbazine, prednisolone, bleomycin, vinblastine, dacarbazine, etoposide, epirubicin, cisplatin cisplatin), capecitabine, oxaliplatin, and the like.

The anti-cancer adjuvant composition may further include at least one active ingredient exhibiting the same or similar function in addition to including the complex extract of fragrant rich and cheoncho as an active ingredient. 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 intrathecal injection, intracerebrovascular injection or chest injection It can be administered by intravenous 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 dosage of the anticancer adjuvant is about 0.0001 to 1000 mg/kg, preferably 1 to 100 mg/kg, and it is preferable to administer once or several times a day in divided doses, but the patient's weight, age, sex, health condition, The range varies according to diet, administration time, administration method, excretion rate, and severity of disease. The anticancer adjuvant of the present invention can be administered in various parenteral formulations during actual clinical administration. is prepared Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for the suppository, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogeratin and the like may be used.

In addition, the present invention provides a method for preventing or treating cachexia (cachexia) comprising administering the pharmaceutical composition for preventing or treating cachexia according to the present invention to a patient.

The treatment method of the present invention comprises administering to a subject a therapeutically effective amount of the pharmaceutical composition. A specific therapeutically effective amount for a specific individual depends on the type and degree of response to be achieved, the specific composition, including whether other agents are used as the case may be, the age, weight, general health condition, sex and diet of the individual, the time of administration, It is preferable to apply differently according to various factors including the route of administration and secretion rate of the composition, treatment period, drugs used together with or concurrently used with the specific composition, and similar factors well known in the medical field. Therefore, the effective amount of the composition suitable for the purpose of the present invention is preferably determined in consideration of the above.

The patient is applicable to any mammal, and the mammal includes domestic animals such as cattle, pigs, sheep, horses, dogs and cats as well as humans and primates.

The method for preventing or treating cachexia of the present invention may be a method for simultaneously preventing or treating cachexia caused by cancer and cancer.

Hereinafter, the present invention will be described in more detail by the following examples. However, the following examples are merely illustrative of the present invention, and the contents of the present invention are not limited by the following examples.

<Example 1> Preparation of composite extracts of fragrant rich and cheoncho

A herbal composite extract containing Cyperi Rhizoma and Zanthoxyli Pericarpium was prepared by hot water extraction by mixing Cyperi Rhizoma and Zanthoxyli Pericarpium in a weight ratio of 1:1. Specifically, after cleaning and washing Hyangbuja and Cheoncho herbs, 250 g of Hyangbuja and 250 g of Cheoncho were mixed, put in 1L of distilled water, and heated at 100 ° C. for 2 hours to make 500 ml. The whole decoction was freeze-dried to prepare a powdered extract of Hyangbuja and Cheoncho (Example 1, HC).

In addition, 500 g of Hyangbuja and 500 g of Cheoncho were prepared using the same method as above to prepare a single extract of Hyangbuja and a single extract of Cheoncho.

At this time, the yields of the extracts of Cheoncho and Hyangbuja were 15.70% and 14.15%, respectively. The extract powder was dissolved in tertiary distilled water, and then 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 cancerous cachexia, obesity/cancer comorbidity animal models were prepared.

Specifically, 7-week-old C57bl/6j mice were fed a high-fat diet for 5 weeks, and then C57bl/6j-derived melanoma cells, B16BL6 cells, were subcutaneously injected into the mouse's left thigh at 5 weeks to prevent cancer (melanoma) and obesity. caused Thereafter, while feeding all groups with a high-fat diet for an additional 2 weeks, the extract of Example 1, cisplatin (cisplatin, CIS), an anticancer drug widely used in the treatment of melanoma, and the composite extract (HC; oral administration, 3 times a week) ; intraperitoneal administration, once a week) was administered. The control group (high fat diet, HFD) and the disease control group (HFD+B16BL6 injection) were given only a high-fat diet without any injection for 2 weeks after inducing obesity or obesity/cancer, respectively.

<Experimental Example 2> Weight loss improvement effect by cancer cachexia of composite extract

In order to confirm the effect of inducing cancerous cachexia and improving the complex extract, body weight change of mice was measured during a treatment period of 7 weeks in the same manner as in Example 1, and is shown in FIG. 1. In addition, in order to correct for the difference in body weight according to cancer tissue, total body weight, cancer tissue weight, inguinal white adipose tissue (iWAT), and abdominal The weight of visceral fat (epididymal white adipose tissue, eWAT) was measured and compared. The measurement results of each weight are shown in FIG. 2 .

As a result, as shown in FIGS. 1 and 2, in the non-cancer control group (HFD), the weight and white adipose tissue weight increased due to the intake of a high-fat diet, whereas in the obesity / cancer-induced disease control group (HFD+ B16BL6 injection), it was observed that the total body weight was relatively reduced, and in particular, in the case of the group treated with the anticancer drug cisplatin (CIS), it was found that the body weight was reduced more than the disease control group. In addition, as shown in Figure 2, the body weight and white adipose tissue weight excluding cancer tissue were significantly reduced in the disease control group (HFD + B16BL6 injection) compared to the control group (HFD). From these results, it was confirmed that cancer cachexia was induced in an animal model with obesity/cancer comorbidity, and it was confirmed that cancer cachexia was not improved and weight loss rather increased when treated with anticancer drugs.

On the other hand, in the obesity/cancer comorbidity animal model, the body weight of the disease control group (HFD+B16BL6 injection) was significantly reduced by 16% compared to the control group (HFD), while the complex extract (HC) of Example 1 was treated. When this weight loss was suppressed, it increased to a level similar to that of the control group (Fig. 2A). Even in the case of subcutaneous fat (iWAT) and abdominal visceral fat (eWAT) weight, when the complex extract (HC) of Example 1 was treated, the fat reduction by cancer tissue was significantly inhibited compared to the disease control group (HFD + B16BL6 injection) , and it was confirmed that the weight was maintained similarly to that of the control group (HFD) (FIGS. 2C and 2D).

In addition, when the composite extract (HC) of Example 1 was treated in an animal model with obesity/cancer comorbidity, the cancer weight was significantly (p<0.05) reduced compared to the disease control group (FIG. 2B). .

As a result, cisplatin, an anticancer agent, can suppress cancer tissue growth, but cannot suppress weight loss and fat loss caused by cancer tissue and rather worsens, whereas the complex extract (HC) of Example 1 of the present invention has excellent While exhibiting an anticancer effect, it was confirmed that it exhibits an excellent inhibitory effect on cancer cachexia by significantly suppressing weight loss and fat loss caused by cancer tissue.

<Experimental Example 3> Effect of complex extracts on the expression of cancer cell death index factors

In order to measure the effect of the composite extract (HC) of Example 1 of the present invention on the expression of apoptosis factors in the cancer tissue of the animal model, representative Bcl-xl of the mitochondrial inner and outer membrane proteins Bcl-family Changes in the expression level of Bax and the expression level of caspase 3, typically in the caspase cascade, which is a major mechanism of apoptosis, were confirmed using Western blot.

Cancer tissue cells of the animal model were mixed 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 electrolysis in an 8% sodium dodecyl sulfatepolyacrylamide gel. They were separated by electrophoresis and transferred to a nitrocellulose membrane. Membranes were blocked with TBST (10 mM Tris, 150 mM NaCl, and 0.05% Tween20, pH 7.6) containing 5% skim milk for 1 hour at room temperature, washed with TBST, and then incubated 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. Then, the membrane was reacted with a secondary antibody (Amersham Biosciences, Westborough, MA, USA) attached with an appropriate horseradish peroxidase (Jackson Lab.) for 2 hours at room temperature. 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 showed up

As a result, as shown in Figure 3, the ratio of Bax / Bcl-xL and cleaved / pro caspase 3 increased in the composite extract (HC) treatment group compared to the disease control group, indicating that there is an inhibitory effect on cancer through activation of these factors Confirmed.

So far, the present invention has been looked at with respect to its preferred embodiments. Those skilled in the art to which the present invention pertains will be able to understand that the present invention can be implemented in a modified form without departing from the essential characteristics of the present invention. Therefore, the disclosed embodiments should be considered from an illustrative rather than a limiting point of view. The scope of the present invention is shown in the claims rather than the foregoing description, and all differences within the equivalent scope will be construed as being included in the present invention.

Claims (12)

Pharmaceuticals for preventing or treating cancer cachexia, including complex extracts of Cyperi Rhizoma and Zanthoxyli Pericarpium, prepared by hot water extraction by mixing Cyperi Rhizoma and Zanthoxyli Pericarpium at a weight ratio of 1:2 to 2:1 enemy composition. delete delete According to claim 1,
Wherein the composition improves weight loss and fat loss, the pharmaceutical composition. According to claim 1,
The composition exhibits anticancer effect and cancer cachexia inhibitory effect at the same time, a pharmaceutical composition. According to claim 5,
Wherein the anti-cancer effect appears through the activation of one or more factors selected from the group consisting of Bax and caspase 3, the pharmaceutical composition. A health functional food composition for preventing or improving cancerous cachexia, comprising a composite extract of fragrant rich plant and fragrant plant, prepared by hot water extraction by mixing fragrant plant and fern plant in a weight ratio of 1:2 to 2:1. delete A health food composition for preventing or improving cancer cachexia, comprising a composite extract of Hyangbuja and Cheoncho prepared by hot-water extraction by mixing Hyangbuja and Cheoncho in a weight ratio of 1:2 to 2:1. delete An anticancer adjuvant composition comprising the pharmaceutical composition for preventing or treating cancerous cachexia of claim 1. A method for preventing or treating cancer cachexia comprising administering the pharmaceutical composition for preventing or treating cancer cachexia of claim 1 to a non-human subject.

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