JP6626035B2 - Pharmaceutical composition for prevention or treatment of sarcopenia and health food composition for prevention or improvement - Google Patents

Description

  The present invention is characterized in that after producing a saponin degrading enzyme, it contains a novel processed ginseng powder or a processed ginseng extract in which a trace amount of ginsenoside component is increased by hydrolysis using the produced saponin degrading enzyme and an organic acid. The present invention relates to a composition for preventing and treating cancer-related fatigue, which has the effect of ameliorating the most serious cancer-related fatigue among the side effects caused by the cancer itself or associated with the treatment of the cancer. It provides a composition.

  One of the most frequent side effects during or after treatment for cancer is cancer-related fatigue. Cancer-related fatigue (CRF) is described by NCCN (National Comprehensive Cancer Network) as "cancer that interferes with daily life and degrades the quality of life of cancer patients, as well as persistent and subjective symptoms associated with cancer treatment." Sensation of tiredsome "is defined. Cancer-related fatigue (CRF) is distinguished from general fatigue in that it is not alleviated by rest and is not primarily induced by physical activity.

  Cancer-related fatigue (CRF) perceived by cancer patients is very serious, chronic, painful, and not relieved by rest, and many studies have shown that among cancer-related side effects, CRF is a quality of life for cancer patients. Reported that it had the most negative impact on daily life and caused limitations in everyday life.

  Although the incidence of cancer-related fatigue (CRF) during cancer treatment depends on the treatment method applied and the duration, it has been reported that almost all cancer patients experience it. That is, the incidence of cancer-related fatigue (CRF) in cancer patients who have not received anticancer treatment is about 75%, and the incidence of CRF in cancer patients who receive chemotherapy or radiation therapy is reported to be higher. The degree of cancer-related fatigue (CRF) felt by patients was generally greater in patients who received bone marrow transplantation and chemotherapy than in patients who received adjuvant chemotherapy without bone marrow transplantation. CRF) and patients receiving adjuvant chemotherapy generally complain of cancer-related fatigue (CRF) more frequently than patients receiving radiation therapy. (Non-Patent Document 1)

  Various side effects or symptoms starting with cancer and its treatment, including cancer-related fatigue (CRF) (eg, depression, anxiety, pain, nausea, vomiting and insomnia, anemia, etc.) require excessive rest, It results in muscle weakness, muscle atrophy, impaired muscle function and impaired cardiopulmonary function. Inactivity due to bed rest and the like has led to a decline in the patient's basic daily living abilities.

  Pharmacological treatments for cancer-related fatigue (CRF) are often aimed at the public, rather than approaching most causes, and are associated with a decline in physical strength and decline in muscle mass and muscle function that appear together in the course of cancer treatment. Such problems cannot be solved.

  The primary pharmacological activity of Modafinil, a drug associated with improving cancer-related fatigue (CRF), promotes arousal. Modafinil has been shown to be effective in rats (Non-Patent Documents 2 to 3), cats, dogs (Non-Patent Document 4), and non-human primates (Non-Patent Document 5), as well as in sleep apnea syndrome (English bulldog [English] [bulldog] a sleep disordered respiratory model) (Non-patent Document 6), and a model that simulates a clinical situation such as paroxysmal sleep (paroxysmal sleeping dog) (Non-patent Document 4) to promote arousal. . Modafinil is a drug having activity in the central nervous system, and is used for the treatment of pakisun disease (Patent Literature 1), protection of cerebral tissues from ischemia (Patent Literature 2), and treatment of urine and urinary incontinence (Patent Literature 3) ), And for the treatment of sleep apnea syndrome and diseases of central origin (Patent Document 4).

  Currently, modafinil is undergoing clinical trials in combination with docetaxel (Docetaxel-Based Chemotherapy) for patients with metastatic breast and prostate cancers complaining of cancer-related fatigue (CRF), and solid cancers complaining of cancer-related fatigue (CRF) Clinical research as a therapeutic agent for cancer-related fatigue (CRF) is being carried out by performing combined administration of radiation therapy (Radiation Therapy) on patients (Non-Patent Document 7).

  The main functional component of ginseng is a ginseng saponin called 'ginsenoside', which is a specially classified ginseng saponin among various saponins in the plant kingdom. Among the ginseng components, saponin is an anti-cancer, anti-allergic, anti-inflammation, as well as central depressant and mentally stable, analgesic, memory improvement, liver disorder treasure, protein and lipid synthesis promotion, anti-diabetes, anti-stress, antioxidant active substance production It has pharmacological effects such as promotion, immunomodulation, inhibition of platelet aggregation, and anti-aging effect.

  On the other hand, saponins such as ginsenosides Rb1, Rb2, and Rc, which are main components exhibiting the pharmacological effects of ginseng, are known. However, it is known that components that substantially suppress anticancer activity or metastasis of cancer cells or antiallergic activity are saponins of compound K (comp K), ginsenoside Rh1, Rh2, and Rg3, which are contained in a very small amount of ginseng. Have been.

  Among ginsenosides known to date as cancer-related fatigue (CRF) effects, ginsenoside Rh2 is known as a composition for preventing or treating cancer-related fatigue (Patent Document 5), and Rg3 is a cancer cell-removing patient fatigue reducing effect ( Non-patent document 8), although not dependent on the volume, reported an effect on anti-fatigue when ginsenoside Rg3 was administered intranasally (Non-patent document 9). However, there is no patent or research literature on the synergistic cancer-related fatigue (CRF) effect according to these ginsenoside Rh2 and / or Rg3 combinations and contents.

  In general, unlike general fatigue, which recovers from rest, pharmacotherapy for cancer-related fatigue (CRF) is often aimed at a public effect rather than approaching most causes, and in the course of cancer treatment. Problems such as a decline in physical strength and a decline in muscle mass and muscle function that appear together cannot be solved. Recently, for cancer patients receiving chemotherapy or radiation therapy, the most prominent motive for the cause of cancer-related fatigue (CRF) is the increased activity of pro-inflammatory cytokines and intramuscular It has been reported that Glycogen synthesis is reduced.

  Here, the present inventors produced saponin degrading enzyme, and then extracted the processed ginseng powder or processed ginseng in which the trace amounts of ginsenoside components, Rh2 and Rg3, were increased by using the produced saponin degrading enzyme and hydrolysis with an organic acid. The present invention has been accomplished by clarifying that a composition characterized by containing a substance is very effective in preventing and treating cancer-related fatigue (CRF).

US Patent No. 5,180,745 US Patent No. 5,391,576 US Patent No. 5,401,776 US Patent No. 5,612,379 China Registered Patent No. 101612159 Korean Registered Patent No. 992800

Ikjung, 2010 Touret et al. , 1995 Edgar and Seidel, 1997 Shelton et al. , 1995 Hernant et al. , 1991 Panckeri et al. , 1996 J. Clin. Oncol. 30, 2012 Kou Xiao-ge et al. , National Medical Frontiers of China, 2010, Abstract. Wenyan et al. , 2008

  After producing saponin-degrading enzyme, the present inventors use processed saponin-degrading enzyme and hydrolysis with an organic acid to increase ginsenoside content in processed ginseng powder or ginseng extract to improve cancer-related fatigue. Discovered the fact that it will help.

  Accordingly, the present invention provides a ginseng powder or ginseng extract in which a small amount of ginsenoside component is increased by using a saponin degrading enzyme and hydrolysis with an organic acid after producing a saponin degrading enzyme effective for cancer-related fatigue. Its purpose is to provide a composition.

  The present invention relates to a ginseng powder or ginseng in which a small amount of ginsenoside component is increased by using a saponin decomposing enzyme produced by the production method of Patent Document 6 and then hydrolyzing with the produced saponin decomposing enzyme and an organic acid. The present invention relates to a composition for preventing and treating cancer-related fatigue of an extract.

  That is, the pharmaceutical composition for preventing or treating cancer-related fatigue of the present invention comprises the steps of (a) inoculating Aspergillus niger into a medium composed of ginseng powder and bran; Culturing the bacteria, (c) the step (b), purifying the culture with an ultrafiltration membrane, (d) the step (c), separating the enzyme from the purified product, and (e) ginseng. (D) adding the enzyme to powder, red ginseng powder, ginseng extract, or red ginseng extract; (f) fermenting the additive in step (e); and (g) fermenting the additive. Separating the fermented product, (h) the step (g), concentrating the supernatant, and (i) the step (h) removing the concentrate from acetoic acid. Reacting with one or more organic acids selected from the group consisting of lactic acid, citric acid, malic acid, and tartaric acid; and (j) neutralizing and filtering, purifying, concentrating, and drying the reaction product in step (i). The present invention relates to a pharmaceutical composition containing the ginseng extract produced in the step of:

  The composition of the present invention is characterized by containing ginsenoside Rh2 and Rg3, and is more synergistically induced by an anticancer agent with such a mixed composition of Rh2 and Rg3 than a composition containing Rh2 or Rg3 alone. It has the effect of remarkably improving cancer-related fatigue.

  The content of the ginsenosides Rh2 and Rg3 is preferably 0.2 to 30% by weight, more preferably 0.5 to 30% by weight, and most preferably 1 to 20% by weight.

  After producing the saponin degrading enzyme of the present invention, the processed ginseng powder or processed ginseng extract in which a trace amount of ginsenoside component is increased using the produced saponin degrading enzyme and hydrolysis with an organic acid is used in combination with an existing anticancer agent. When used, it has the effect of ameliorating cancer-related fatigue induced by anticancer drugs.

  Examples of the existing anticancer agent include cisplatin, carboplatin, paraplatin, oxaliplatin, nedaplatin, doxorubicin, taxol, docetaxel, tamoxifen, Kamtober, adolcil, Gleevec, etoposide, zometa, oncobin, lupron, gemza, 5-fluorouracil, and rucobolin. I do.

  After preparing the saponin degrading enzyme of the present invention, a novel processed ginseng powder or processed ginseng extract in which a trace amount of ginsenoside component is increased by using the produced saponin degrading enzyme and hydrolysis with an organic acid is 1 weight of the existing anticancer agent. It is preferred to use 0.1 to 1000 parts by weight based on parts. When the content is within the above range, cancer-related fatigue, which is a side effect caused by the anticancer agent, can be effectively improved.

  After producing the saponin-decomposing enzyme according to the present invention, the saponin-decomposing enzyme contains a processed ginseng powder or a processed ginseng extract in which a trace amount of ginsenoside component is increased by hydrolysis using the produced saponin-degrading enzyme and an organic acid. The pharmaceutical composition for preventing or treating cancer-related fatigue can be formulated into various oral or parenteral dosage forms, but is not limited thereto.

  After producing the saponin-decomposing enzyme according to the present invention, the saponin-decomposing enzyme contains a novel processed ginseng powder or processed ginseng extract in which a trace amount of ginsenoside component is increased by hydrolysis using the produced saponin-degrading enzyme and an organic acid. The composition can be manufactured into health-supporting or health-functional foods such as foods and beverages for the purpose of preventing or improving cancer-related fatigue. In this case, when the composition according to the present invention is used as a food additive, it can be added in an amount of 0.01 to 30% by weight, preferably 0.1 to 10% by weight, based on the raw materials. The mixing amount of the effective component can be appropriately determined depending on the purpose of use. However, in the case of long-term ingestion for the purpose of health and hygiene, or for the purpose of health regulation, since the amount is below the above range or there is no problem in terms of safety, The effective component can be used in an amount larger than the above range. After producing the saponin degrading enzyme, a composition comprising a novel processed ginseng powder or a processed ginseng extract in which a trace amount of ginsenoside component is increased by hydrolysis using the produced saponin degrading enzyme and an organic acid. The product can be used with other foods or food ingredients and can be used appropriately by conventional methods.

  The composition of the present invention contains a novel processed ginseng powder or processed ginseng extract in which a trace amount of ginsenoside component is increased by using a saponin degrading enzyme and hydrolysis with an organic acid after manufacturing the saponin degrading enzyme. A composition that is effective in preventing or treating cancer-related fatigue.

  After producing the saponin degrading enzyme of the present invention, a composition containing a novel processed ginseng powder or a processed ginseng extract in which a trace amount of ginsenoside component is increased by hydrolysis using the produced saponin degrading enzyme and an organic acid, When ginsenosides Rh2 and Rg3 are simultaneously contained in increased amounts, they exhibit an effect of preventing or treating cancer-related fatigue, which is synergistically superior to a composition containing ginsenoside Rh2 or Rg3 alone.

  In addition, the composition of the present invention has an excellent preventive and therapeutic or ameliorating effect on cancer-related fatigue.

  The present invention provides a novel processed ginseng powder in which a small amount of ginsenoside component is increased by using a saponin decomposing enzyme produced by the production method of Patent Document 6 and then hydrolyzing with the produced saponin decomposing enzyme and an organic acid or The present invention relates to a composition of a ginseng extract for preventing or treating cancer-related fatigue.

  Hereinafter, the configuration of the present invention will be described in more detail with reference to specific examples of the present invention. However, the scope of the present invention is not limited only to the description of the embodiments, and can be modified and implemented by those skilled in the art without departing from the technical idea of the present invention. It is obvious for a person skilled in the art to belong to the range.

<Comparative Example 1: Production of ginseng powder>
After drying 200 g of ginseng for 6 years with hot air, it was pulverized to obtain 60 g of ginseng powder.

<Comparative Example 2: Production of ginseng concentrate>
After 6 g of ginseng 200 g was dried with hot air, 1 L of 70% spirit was added, and the mixture was stirred and extracted at 70 ° C. for 8 hours, and then filtered and concentrated to obtain 50 g of a ginseng concentrate.

<Comparative Example 3: Production of ginseng concentrate liquid powder>
Sixty-year-old ginseng 200 g was dried with hot air, 1 L of 70% spirit was added, and the mixture was stirred and extracted at 70 ° C. for 8 hours.

<Comparative Example 4: Production of red ginseng>
200 g of ginseng for 6 years was steamed and dried at 98 ° C. for 1 hour, and then pulverized to obtain 40 g of red ginseng powder.

<Comparative Example 5: Production of red ginseng concentrate>
After steaming 200 g of ginseng for 6 hours at 98 ° C. for 1 hour, adding 1 L of 70% spirit and stirring and extracting at 70 ° C. for 8 hours, filtering and concentrating to obtain 30 g of red ginseng concentrate. Obtained.

<Comparative Example 6: Production of powdered red ginseng concentrate>
6 g of ginseng 200g was steamed and dried at 98 ° C for 1 hour, 1L of 70% spirit was added, stirred at 70 ° C for 8 hours, filtered, concentrated, dried and concentrated to 25g of red ginseng A liquid powder was obtained.

<Comparative Example 7: Production of ginseng powder + Rh2 0.2% + Rg3 0.3%>
99.5 g of the ginseng powder of Comparative Example 1 was mixed with 0.2 g of Rh2 and 0.3 g of Rg3.

<Comparative Example 8: Red ginseng powder + Rh2 0.2% + Rg3 0.3% production>
9 g of the red ginseng powder of Comparative Example 4 was mixed with 0.2 g of Rh2 and 0.3 g of Rg3.

<Comparative Example 9: Red ginseng powder + 1% Rh2 production>
99 g of the red ginseng powder of Comparative Example 4 was mixed with 1 g of Rh2.

<Comparative Example 10: Red ginseng powder + Rg3 1% production>
99 g of the red ginseng powder of Comparative Example 4 was mixed with 1 g of Rg3.

<Comparative Example 11: Production of red ginseng powder + Rh2 0.5% + Rg3 0.5%>
99 g of red ginseng powder of Comparative Example 4 was mixed with 0.5 g of Rh2 and 0.5 g of Rg3.

<Comparative Example 12: Modafinil production>
Modafinil 100 mg / kg. B. The mixture was mixed with PBS at a concentration of W and orally administered by 100 μl daily.

<Example 1: Production of processed ginseng powder using ginseng powder>
250 g of ginseng powder and 750 g of bran are put and sterilized by a high-pressure steam sterilizer at 121 ° C. and 1.5 atm. After 2 L of sterile water is added to the sterilized medium and mixed, an Aspergillus niger suspension (5 × 10 ⁵ spores / g of medium) is cultured at 28 ° C. for 7 days. When the culture is completed, a 0.02 M sodium acetate buffer solution is added, mixed, and the medium is filtered. The filtered culture solution is filtered and concentrated using an ultrafiltration membrane (100 KDa or more) to obtain 60 g of an enzyme solution. After adding 30 g of the enzyme solution to 200 g of the ginseng powder of Comparative Example 1 and culturing at 28 ° C. for 18 hours, alcohol is added to precipitate the enzyme, and the supernatant is concentrated. After 2 L of purified water was added to 200 g of the concentrate, 250 g of citric acid was added, and the mixture was stirred at 50 ° C. for 18 hours. When the reaction was completed, 70% spirit was added, filtered and concentrated to obtain 200 g of ginseng powder.

<Example 2: Production of processed ginseng concentrate using ginseng concentrate>
250 g of ginseng powder and 750 g of bran are put and sterilized by a high-pressure steam sterilizer at 121 ° C. and 1.5 atm. After adding 2 L of sterilized water to a sterilized medium and mixing, a suspension of Aspergillus niger (5 × 10 ⁵ spores / g of medium) is inoculated, and cultured at 28 ° C. for 7 days. When the culture is completed, a 0.02 M sodium acetate buffer solution is added, mixed, and the medium is filtered. The filtered culture solution is filtered and concentrated using an ultrafiltration membrane (100 KDa or more) to obtain 60 g of an enzyme solution. After adding 30 g of the enzyme solution to 200 g of the ginseng concentrate of Comparative Example 2 and culturing at 28 ° C. for 18 hours, alcohol is added to precipitate the enzyme, and the supernatant is concentrated. After adding 2 L of purified water to 200 g of the concentrate, 250 g of citric acid was added, and the mixture was stirred at 50 ° C. for 18 hours. When the reaction was completed, 70% spirit was added, filtered and concentrated to obtain 190 g of processed ginseng concentrate.

<Example 3: Production of processed ginseng concentrate powder using ginseng concentrate powder>
250 g of ginseng powder and 750 g of bran are put and sterilized by a high-pressure steam sterilizer at 121 ° C. and 1.5 atm. After 2 L of sterile water is added to the sterilized medium and mixed, an Aspergillus niger suspension (5 × 10 ⁵ spores / g of medium) is inoculated, and cultured at 28 ° C. for 7 days. When the culture is completed, a 0.02 M sodium acetate buffer solution is added, mixed, and the medium is filtered. The filtered culture solution is filtered and concentrated using an ultrafiltration membrane (100 KDa or more) to obtain 60 g of an enzyme solution. After adding 30 g of the enzyme solution to 200 g of the ginseng concentrate liquid powder of Comparative Example 3 and culturing at 28 ° C. for 18 hours, alcohol is added to precipitate the enzyme, and the supernatant is concentrated. 2 L of purified water was added to 200 g of the concentrate, 250 g of acetic acid was added, and the mixture was stirred at 50 ° C. for 8 hours. When the reaction was completed, 70% alcohol was added, filtered, concentrated and dried to obtain 195 g of processed ginseng concentrated liquid powder.

<Example 4: Production of processed red ginseng powder using red ginseng powder>
250 g of ginseng powder and 750 g of bran are put and sterilized by a high-pressure steam sterilizer at 121 ° C. and 1.5 atm. After 2 L of sterile water is added to the sterilized medium and mixed, an Aspergillus niger suspension (5 × 10 ⁵ spores / g of medium) is inoculated, and cultured at 28 ° C. for 7 days. When the culture is completed, a 0.02 M sodium acetate buffer solution is added, mixed, and the medium is filtered. The filtered culture solution is filtered and concentrated using an ultrafiltration membrane (100 KDa or more) to obtain 60 g of an enzyme solution. After adding 30 g of the enzyme solution to 200 g of the red ginseng powder of Comparative Example 4 and culturing at 28 ° C. for 18 hours, alcohol is added to precipitate the enzyme, and the supernatant is concentrated. 2 L of purified water was added to 200 g of the concentrate, 250 g of acetic acid was added, and the mixture was stirred at 50 ° C. for 8 hours. When the reaction was completed, 70% spirit was added, filtered, concentrated and dried to obtain 195 g of processed red ginseng powder.

<Example 5: Production of processed red ginseng concentrate using red ginseng concentrate>
250 g of ginseng powder and 750 g of bran are put and sterilized by a high-pressure steam sterilizer at 121 ° C. and 1.5 atm. After 2 L of sterile water is added to the sterilized medium and mixed, an Aspergillus niger suspension (5 × 10 ⁵ spores / g of medium) is inoculated, and cultured at 28 ° C. for 7 days. When the culture is completed, a 0.02 M sodium acetate buffer solution is added, mixed, and the medium is filtered. The filtered culture solution is filtered and concentrated using an ultrafiltration membrane (100 KDa or more) to obtain 60 g of an enzyme solution. After adding 30 g of the enzyme solution to 200 g of the red ginseng concentrated solution of Comparative Example 5 and culturing at 28 ° C. for 18 hours, alcohol is added to precipitate the enzyme, and the supernatant is concentrated. 2 L of purified water was added to 200 g of the concentrate, 250 g of citric acid was added, and the mixture was stirred at 50 ° C. for 18 hours. When the reaction was completed, 70% spirit was added, filtered and concentrated to obtain 190 g of processed red ginseng concentrate.

<Example 6: Production of processed red ginseng concentrated powder using red ginseng concentrated powder>
250 g of ginseng powder and 750 g of bran are put and sterilized by a high-pressure steam sterilizer at 121 ° C. and 1.5 atm. After 2 L of sterilized water is added to the sterilized medium and mixed, the suspension is inoculated with an Aspergillus niger suspension (5 × 10 ⁵ spores / g of medium) and cultured at 28 ° C. for 7 days. When the culture is completed, a 0.02 M sodium acetate buffer solution is added, mixed, and the medium is filtered. The filtered culture solution is filtered and concentrated using an ultrafiltration membrane (100 KDa or more) to obtain 60 g of an enzyme solution. After adding 30 g of the enzyme solution to 200 g of the red ginseng concentrated liquid powder of Comparative Example 6 and culturing at 28 ° C. for 18 hours, alcohol is added to precipitate the enzyme, and the supernatant is concentrated. 2 L of purified water was added to 200 g of the concentrate, 250 g of acetic acid was added, and the mixture was stirred at 50 ° C. for 8 hours. When the reaction was completed, 70% spirit was added, filtered, concentrated and dried to obtain 195 g of processed red ginseng concentrated liquid powder.

  Table 1 below shows the contents of ginsenoside Rh2 and Rg3 contained in the products of Examples and Comparative Examples of the present invention analyzed by the method disclosed in Patent Document 6. After producing saponin degrading enzyme for ginseng powder and red ginseng powder corresponding to Examples 1 to 6 of the present invention, a novel ginsenoside component increased by using the produced saponin degrading enzyme and hydrolysis with an organic acid. It was confirmed that the processed ginseng powder or the processed ginseng extract contained Rh2 and Rg3 in larger amounts than those of the ginseng powder and the red ginseng powder, which are the reaction target substances. Comparative Examples 7 to 11 show that Rh2 and Rg3 were simply added to ginseng powder and red ginseng powder which were not treated with saponin degrading enzyme and organic acid as in Examples of the present invention. And an Rg3 content, which were manufactured to compare the effects of improving cancer-related fatigue.

<Experimental example 1: Effect of composition for improving fatigue caused by cancer>
The experimental animals received Balb / c-nu / nu mouse female, weighing 20 ± 2 g, 6 weeks old, supplied by Orient Co., Ltd. at a temperature of 23 ± 1 ° C., a relative humidity of 55 ± 15%, and at 12-hour intervals. The animals were bred in an animal breeding room where light and darkness were controlled, and they were allowed to freely ingest a feed (Orient Co., Ltd.) for one week, purified, and then observed macroscopic symptoms. 100 μl of HT-29 (5 × 10 ⁶ cells / mouse) cells were implanted subcutaneously in the flank into Balb / c nu / nu mouse purified for one week and then visually observed. When the tumor size reached 150 mm ³ , the mice were randomly divided into groups and drug administration was started. Spontaneous locomotor activity (Running wheel activity) and forced locomotion (Swimming test) were measured after the administration of the anticancer drug and drug was completed. The amount of Glycogen synthesized in the muscle was homogenized from the tissue collected from the thigh on the last autopsy day. After that, the analysis was performed through the ELISA kit.

-Running wheel activity (Running distance = meter / 10min)
Locomotor activity was measured through a running wheel activity as a parameter of cancer related fatigue (CRF). The number of turns after running for a total of 10 minutes with a Wheel of 300φ was measured, and this was converted as a distance (meter).

^* Running distance = circumference (30 cm x 3.14) x number of turns / 10 min

-Swimming test
After filling warm water (23 ± 1 ° C.) in a transparent constant temperature water bath (500 mm × 500 mm × 400 mm) capable of maintaining a constant temperature and water depth, forced swimming (FS) was performed. Immediately after the weakness determination, the total swimming time was recorded.

-Calculation of increase rate (%)
Average of Example or Comparative Example treatment group−Average of control × 100
Average of Normal group-Average of control

  All the examples and comparative examples were prepared by diluting them into phosphate buffered saline (PBS) by volume, and then gavaged orally by using an oral administration needle (sonde). The dose volume was calculated by mixing and diluting with PBS at a concentration of 100 mg / kg body weight and administering 100 μl / 20 g according to the body weight measured on the day of administration, and the administration time of the test substance was once a day, around 10 am For 4 weeks. The groups for evaluation in this experimental example are as shown in Table 2.

For the verification of the significance of all the following experimental examples, p-values were compared at a significance level of 0.05 by the Student's T-test analysis method.
^# : P <0.05 vs. Normal group ^* : p <0.05 vs Control group
^## : p <0.01 vs. normal group ^** : p <0.01 vs. control group
^## : p <0.001 vs Normal group ^*** : p <0.001 vs Control group

  The following Table 3 shows the results of Experimental Example 1, in which the HT-29 colon cancer cell line was xenografted in an animal model, and the Example and Comparative Examples were administered together for 4 weeks, and the distance ran for 10 minutes. Table 4 shows the results of comparative evaluation of spontaneous locomotion due to cancer, and Table 4 shows the results of comparative evaluation of forced locomotion due to cancer during swimming time. After preparing saponin-degrading enzymes for ginseng powder and red ginseng powder corresponding to Examples 1 to 6 of the present invention, processed ginseng having a small amount of ginsenoside component increased by hydrolysis using the produced saponin-degrading enzymes and organic acids. The powder or the processed ginseng extract showed a spontaneous momentum increase rate of 62.6 to 96.2% and a forced momentum increase rate of 63.0 to 98.0%, indicating that the reaction of Examples 1 to 6 of the present invention. The ginseng powder and the red ginseng powder of Comparative Examples 1 to 6 corresponding to the target substance show a locomotor activity of 3.2 to 18.8% and a rate of increase in the amount of exercise due to improvement in cancer-related fatigue, which is superior to the rate of increase in forced exercise. . In addition, the ginseng or ginseng extract of Examples 1 to 6 of the present invention was obtained by adding Rh2 and Rg3 to the ginseng powder and red ginseng powder of Comparative Examples 1 and 4, and adding Rh2 and Rg3 as in Example 1. Cancers of Comparative Examples 7 and 8 produced by increasing the Rg3 content to 0.2% by weight and 0.3% by weight, respectively, in which the rate of increase in spontaneous locomotion and forced locomotion is better than 20.8-30.6% The increase in the amount of exercise due to the improvement of the related fatigue indicates that the effect of the ginseng or the extract of the ginseng of the present invention to increase the amount of exercise due to the improvement of the cancer-related fatigue is increased by other effective components other than Rh2 and Rg3. . On the other hand, Comparative Examples 9 to 11 are compositions prepared by additionally mixing 1 g of Rh2, 1 g of Rg3, and (0.5 g of Rh2 + 0.5 g of Rg3) with 99 g of red ginseng powder, respectively. In comparison with Comparative Example 10 (containing 1% by weight of Rg3) and Comparative Example 11 (containing 0.5% by weight of Rh2 + 0.5% by weight of Rg3), a superior therapeutic effect on cancer-related fatigue is shown. It can be confirmed that, when Rh2 or Rg3 are administered in combination, they have a synergistic improvement in cancer-related fatigue or a therapeutic effect when Rh2 or Rg3 is administered alone.

<Experimental example 2: Effect of fatigue improving composition by anticancer agent>
The evaluation was performed under the same conditions as in the method of Experimental Example 1, except that all the examples and comparative examples were compared and evaluated under the conditions where the anticancer agent was treated. The anticancer drug treated 5-FU at a concentration of 30 mg / kg three times a week. The groups for evaluation in this experimental example are as shown in Table 5.

  Table 6 below shows the results of Experimental Example 2. In an animal model obtained by xenotransplantation of the HT-29 colorectal cancer cell line, an anticancer agent and each of Examples and Comparative Examples were administered together for 4 weeks, followed by final necropsy. It is the result of comparing the amount of synthesis of Glycogen in the muscle collected from the thigh of the hind leg on the day. As a result, as compared with the Normal group, the amount of synthesized Glycogen in the Xenograft group xenografted with colorectal cancer decreased by 39.2%, and the control group to which the anticancer drug was administered also decreased by 51.4% as compared to the Normal group. However, as a result of co-administering Examples 1 to 6 together with anticancer drug treatment, it was confirmed that the amount of synthesized glycogen increased significantly as compared with the Control group to which the anticancer agent was administered, and Comparative Example 12 ( Modafinil) did not show any significant change compared to the examples and the like. The rate of increase in the amount of synthesized glycogen in each Example and Comparative Example is as shown in Table 6.

<Experimental example 3: Effect of fatigue improving composition by radioactive treatment>
The evaluation was performed under the same conditions as in the method of Experimental Example 1, except that the respective examples and comparative examples were comparatively evaluated under the condition of radiation treatment. Radiation was treated with 10 Gy three times a week. The groups for evaluation in this experimental example are as shown in Table 7.

  Table 8 below shows the results of Experimental Example 3. In the animal model in which the HT-29 colorectal cancer cell line was xenografted, radiation and each Example and Comparative Example were administered together for 4 weeks, followed by final necropsy. It is the result of comparing the amount of synthesis of Glycogen in the muscle collected from the thigh of the hind leg on the day. As a result, the amount of synthesized Glycogen in the Xenograft group xenografted with colorectal cancer was reduced by 36.5% compared to the Normal group, and the control group treated with radiation was also reduced by 51.4% compared to the Normal group. However, as a result of co-administering Examples 1 to 6 together with the radiation treatment, it was confirmed that the amount of synthesized glycogen increased as compared with the control group treated with the radiation, and Comparative Example 1, In the group to which 4, 7, 9, 10, 11, 12 (modafinil) was co-administered, no significant change was observed as compared with the examples and the like. The rate of increase in the amount of synthesized glycogen in each Example and Comparative Example is as shown in Table 8.

Claims (2)

In cancer-related fatigue, spontaneous exercise, forced exercise, a pharmaceutical composition that increases the amount of glycogen synthesis in muscle,
Contains ginseng extract,
The pharmaceutical composition, wherein the ginseng extract contains ginsenoside Rh2 and Rg3 at 0.5 to 30% by weight, respectively. In a cancer-related fatigue, spontaneous exercise, forced exercise, a health functional food composition that increases the amount of glycogen synthesis in muscle,
Contains ginseng extract,
The health functional food composition, wherein the ginseng extract contains ginsenoside Rh2 and Rg3 at 0.5 to 30% by weight, respectively.