JP2022091992A - Pharmaceutical composition for prevention or treatment of sarcopenia and health functional food composition for prevention or improvement - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide pharmaceutical compositions for the prevention or treatment of cancer-related fatigue.

SOLUTION: Provided is a pharmaceutical composition for the prevention or treatment of cancer-related fatigue, the prevention or treatment of cancer-related fatigue being due to an increase in spontaneous exercise amount and forced exercise amount, the composition containing Panax ginseng extract produced in the steps of: (a) inoculating Aspergillus niger into a medium composed of Panax ginseng powder and bran; (b) culturing the fungus of the step (a); (c) purifying the culture of the step (b) with an ultrafiltration membrane; (d) separating an enzyme from the purified product of the step (c); (e) adding the enzyme of the step (d) to Panax ginseng powder, Red ginseng powder, Panax ginseng extract, or Red ginseng extract; (f) fermenting the additive of the step (e); (g) separating the fermented product of the step (f); (h) concentrating the supernatant of the step (g); (i) reacting the concentrate of the step (h) with one or more organic acids selected from the group consisting of acetic acid, lactic acid, citric acid, malic acid, and tartaric acid; and (j) neutralizing, filtering, purifying, concentrating and drying the reactant of the step (i), the Panax ginseng extract containing ginsenosides Rh2 and Rg3 in an amount of 1 to 20 wt.%, respectively. The cancer-related fatigue includes muscle weakness, muscle atrophy, and fatigue due to muscle function damage (cancer cachexia-related fatigue).

SELECTED DRAWING: None

COPYRIGHT: (C)2022,JPO&INPIT

Description

The present invention is characterized by containing a novel processed ginseno 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 after producing the saponin-degrading enzyme. It relates to a composition for preventing and treating cancer-related fatigue, and has an effect of improving the most serious cancer-related fatigue among the side effects caused by the cancer itself or appearing in connection with the treatment of 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 a persistent and subjective association with cancer treatment that interferes with daily life and worsens the quality of life of cancer patients by NCCN (National Comprehensive Cancer Network). It is defined as "a feeling of tiredsome". Cancer-related fatigue (CRF) can be distinguished from general fatigue in that it is not relieved by rest and is not primarily induced by physical activity.

Cancer-related fatigue (CRF) felt by cancer patients is very serious, chronic, painful, and not relieved by rest, and many studies describe that CRF is the quality of life for cancer patients among cancer-related side effects. It reports that it has the most negative effects on cancer and imposes restrictions on daily life.

The incidence of cancer-related fatigue (CRF) during cancer treatment varies depending on the treatment method and duration applied, but has been reported to be experienced by almost all cancer patients. That is, it is reported that 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 higher. The degree of cancer-related fatigue (CRF) felt by patients is generally greater in patients receiving bone marrow transplantation and chemotherapy than in patients receiving immunoreinforcing agent (adjuvant) chemotherapy without bone marrow transplantation (adjuvant). Patients who present with CRF) and receive adjuvant chemotherapy generally complain of cancer-related fatigue (CRF) more frequently than those who receive radiation therapy. (Non-Patent Document 1)

Various side effects or symptoms that begin with cancer and its treatment process, including cancer-related fatigue (CRF) (eg, depression, anxiety, pain, nausea, vomiting and insomnia, anemia, etc.) require excessive rest. It causes muscle weakness, muscle atrophy, muscle dysfunction and cardiopulmonary dysfunction. Inactivity, such as bed rest, will further diminish the patient's basic daily living abilities.

Drug therapy for cancer-related fatigue (CRF) is often aimed at a mass effect rather than an approach to the cause for the most part, as well as a decrease in physical fitness and muscle mass and function that are manifested together in the course of cancer treatment. It becomes impossible to solve such a problem.

The primary pharmacological activity of Modafinil, a cancer-related fatigue (CRF) ameliorating drug, promotes wakefulness. Modafinil is found not only in rats (Non-Patent Documents 2-3), cats, dogs (Non-Patent Document 4), and non-human primates (Non-Patent Document 5), but also in sleep apnea syndrome (English Bulldog [English Bulldog]. Bulldog] Promotes wakefulness with models that mimic clinical situations such as sleep-impaired breathing model) (Non-Patent Document 6) and paroxysmal sleep (paroxysmal sleep dog) (Non-Patent Document 4). .. Modafinyl is a drug having activity in the central nervous system, and is used for treatment of Pakisun's disease (Patent Document 1), protection of cerebral tissue from ischemia (Patent Document 2), and treatment of urinary and urinary incontinence (Patent Document 3). ), And described as a useful agent for the treatment of sleep apnea syndrome and diseases of central origin (Patent Document 4).

Modafinyl is currently being administered clinically to patients with metastatic breast cancer and prostate cancer who complain of cancer-related fatigue (CRF) in combination with docetaxel-Based Chemotherapy, and is a solid cancer that complains of cancer-related fatigue (CRF). Clinical research is underway as a therapeutic agent for cancer-related fatigue (CRF) by administering it to patients in combination with radiation therapy (Non-Patent Document 7).

The main functional component of ginseng is ginseng saponin called'ginsenoside', which is named by specially classifying only ginseng saponin among various saponins in the plant kingdom. Among the ginseng components, saponin has anticancer, antiallergic, anti-inflammatory, central suppression and mental stability, analgesia, memory improvement, liver damage treasure trove, protein and lipid synthesis promotion, anti-diabetes, anti-stress, anti-oxidation active substance production. It has pharmacological effects such as promotion, immunomodulation, suppression of platelet aggregation, and anti-aging action.

On the other hand, saponins such as ginsenosides Rb1, Rb2, and Rc, which are the main components showing the pharmacological efficacy of ginseng, are known. However, it is known that the component related to the anticancer action or the metastasis of cancer cells or the antiallergic action is compound K (comp K), ginsenoside Rh1, Rh2, Rg3 saponin contained in a very small amount of ginseng. Has been done.

Among ginsenosides known as cancer-related fatigue (CRF) effects, ginsenoside Rh2 is known as a cancer-related fatigue preventive or therapeutic composition (Patent Document 5), and Rg3 has a cancer cell removal patient fatigue reducing effect (Patent Document 5). Although not dose-dependent with Non-Patent Document 8), an effect on anti-fatigue was reported 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 associations and contents.

In general, unlike general fatigue, which recovers with rest, drug therapy for cancer-related fatigue (CRF) is often aimed at a mass effect rather than an approach to the cause, and in the course of cancer treatment. It becomes impossible to solve problems such as weakness of physical strength and deterioration of muscle mass and function that appear together. Recently, for cancer patients receiving chemotherapy or radiation therapy, the most probable mechanism for the manifestation of cancer-related fatigue (CRF) is increased activity of pro-inflammation cytokines and intramuscular. Decreased glycogen synthesis has been reported.

Here, the present inventors have produced a saponin-degrading enzyme, and then hydrolyzed with the produced saponin-degrading enzyme and an organic acid to extract a processed ginseno powder or processed ginseng powder in which trace amounts of ginsenoside components Rh2 and Rg3 are increased. The present invention has been completed by demonstrating that the composition comprising the substance is very effective in the prevention and treatment of cancer-related fatigue (CRF).

US Registered Patent No. 5,180,745 US Registered Patent No. 5,391,576 US Registered Patent No. 5,401,776 US Registered 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 the saponin-degrading enzyme, the present inventors use the processed saponin-degrading enzyme and the processed ginsenoside component in which a trace amount of ginsenoside component is increased by hydrolysis with the produced saponin-degrading enzyme and an organic acid to improve cancer-related fatigue. I found the fact that it helps.

Therefore, the present invention is a processed ginseno powder or processed ginseno extract in which a trace amount of ginsenoside component is increased by producing a saponin-degrading enzyme effective for cancer-related fatigue and then hydrolyzing with the produced saponin-degrading enzyme and an organic acid. It is an object thereof to provide a composition.

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

That is, the pharmaceutical composition for preventing or treating cancer-related fatigue of the present invention comprises (a) injecting Aspergillus niger into a medium composed of carrot powder and a syrup, and (b) the step (a). The step of culturing the fungus, (c) the step (b) the step of purifying the culture with an ultrafiltration, (d) the step (c) the step of separating the enzyme from the purified product, (e) ginseng. The step (d) adding the enzyme to the powder, the red ginseng powder, the ginseng extract, or the red ginseng extract, (f) the step (e) the step of fermenting the additive, (g) the step (f). A group consisting of (h) the step of separating the fermented product, (h) the step (g) the step of concentrating the supernatant, (i) the step (h) the concentrate consisting of acetic acid, lactic acid, citric acid, apple acid, and tartrate acid. A pharmaceutical containing a ginseng extract produced in a step of reacting with one or more organic acids selected from the above, and (j) the step (i) of neutralizing and filtering, purifying, concentrating and drying the reactants. It relates to a composition.

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

The contents of ginsenosides Rh2 and Rg3 are 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 ginsenoside powder or the processed ginseno extract in which a trace amount of ginsenoside component is increased by using the produced saponin-degrading enzyme and hydrolysis with an organic acid can be used in combination with an existing anticancer agent. When used, it has the effect of improving cancer-related fatigue induced by anticancer agents.

Examples of the existing anticancer agents include cisplatin, carboplatin, paraplatin, oxaliplatin, nedaplatin, doxorubicin, taxol, docetaxel, tamoxyphene, camtobel, adolcil, gleevec, etoposide, zometa, oncobin, rupron, gemza, 5-fluorouracil, lucobolin and the like. do.

After producing the saponin-degrading enzyme of the present invention, a novel processed ginsenoside powder or processed ginseno 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 an existing anticancer agent. It is preferable to use in combination with 0.1 to 1000 parts by weight with respect to the part. When the content is within the above range, cancer-related fatigue, which is a side effect caused by the anticancer drug, can be effectively improved.

After producing the saponin-degrading enzyme according to the present invention, it is characterized by containing a processed ginseno powder or a 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. , Cancer-related fatigue-preventing or therapeutic pharmaceutical compositions can be formulated into a variety of oral or parenteral dosage forms, including but not limited to:

After producing the saponin-degrading enzyme according to the present invention, it is characterized by containing a novel processed ginseno 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. Can be produced as a health supplement or health functional food 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 material. 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, the above amount is below the above range, or there is no problem in terms of safety. The effective amount can be used in an amount exceeding the above range. A composition characterized by containing a novel processed ginseno 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 after producing the saponin-degrading enzyme. The product can be used with other foods or food ingredients and can be used properly by conventional methods.

The composition of the present invention contained a novel processed ginseno powder or processed ginseng extract in which a trace amount of ginsenoside component was increased by using the produced saponin-degrading enzyme and hydrolysis with an organic acid after producing the saponin-degrading enzyme. It is 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 ginsenoside powder or a processed ginseno extract in which a trace amount of ginsenoside component is increased by using the produced saponin-degrading enzyme and hydrolysis with an organic acid can be obtained. The simultaneous increased amount of ginsenosides Rh2 and Rg3 exhibits a synergistically superior effect on preventing or treating cancer-related fatigue than compositions in which ginsenosides Rh2 or Rg3 are present alone.

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

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

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 to the description of the examples, and those skilled in the art can perform modifications within a range not deviating from the technical idea of the present invention, and such modifications can be carried out by those skilled in the art. It is obvious to those skilled in the art that it belongs to the range.

<Comparative Example 1: Manufacture of carrot powder>
After 6 years, 200 g of ginseng was dried with hot air and then pulverized to obtain 60 g of ginseng powder.

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

<Comparative Example 3: Production of Ginseng Concentrate Powder>
After 6 years, 200 g of ginseng was dried with hot air, 1 L of 70% alcohol was added, and the mixture was stirred and extracted at 70 ° C. for 8 hours, then filtered, concentrated and dried to obtain 30 g of ginseng concentrate powder.

<Comparative example 4: Production of red ginseng>
After steaming and drying 200 g of 6-year-old ginseng at 98 ° C. for 1 hour, the mixture was pulverized to obtain 40 g of red ginseng powder.

<Comparative Example 5: Production of Red Ginseng Concentrate>
After steaming 200 g of 6-year-old ginseng at 98 ° C for 1 hour and drying it, add 1 L of 70% alcohol and stir-extract at 70 ° C for 8 hours, then filter and concentrate to obtain 30 g of red ginseng concentrate. Obtained.

<Comparative Example 6: Production of Red Ginseng Concentrate Powder>
After steaming 200 g of 6-year-old ginseng at 98 ° C for 1 hour and drying it, add 1 L of 70% alcohol and stir-extract at 70 ° C for 8 hours, then filter, concentrate and dry to concentrate 25 g of red ginseng. A liquid powder was obtained.

<Comparative Example 7: Ginseng powder + Rh2 0.2% + Rg3 0.3% production>
Rh2 0.2 g and Rg3 0.3 g were mixed with 99.5 g of the carrot powder of Comparative Example 1.

<Comparative Example 8: Red ginseng powder + Rh2 0.2% + Rg3 0.3% production>
Rh2 0.2 g and Rg3 0.3 g were mixed with 99.5 g of the red ginseng powder of Comparative Example 4.

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

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

<Comparative Example 11: Red ginseng powder + Rh2 0.5% + Rg3 0.5% production>
Rh2 0.5 g and Rg3 0.5 g were mixed with 99 g of the red ginseng powder of Comparative Example 4.

<Comparative Example 12: Production of modafinil>
Modafinil 100 mg / kg. B. It was mixed with PBS at a concentration of W and orally administered 100 μl daily.

<Example 1: Production of processed ginseng powder using ginseng powder>
Add 250 g of carrot powder and 750 g of bran and sterilize with 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 / medium weight g) is cultured at 28 ° C. for 7 days. When the culture is complete, 0.02 M sodium acetate buffer is added, mixed and then filtered through the medium. 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 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% alcohol was added, filtered and concentrated to obtain 200 g of processed ginseng powder.

<Example 2: Production of processed ginseng concentrate using ginseng concentrate>
Add 250 g of carrot powder and 750 g of bran and sterilize with 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 / medium weight g) is inoculated and cultured at 28 ° C. for 7 days. When the culture is complete, 0.02 M sodium acetate buffer is added, mixed and then filtered through the medium. 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% alcohol 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>
Add 250 g of carrot powder and 750 g of bran and sterilize with 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 / medium weight g) is inoculated and cultured at 28 ° C. for 7 days. When the culture is complete, 0.02 M sodium acetate buffer is added, mixed and then filtered through the medium. 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 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, and the mixture was filtered, concentrated and dried to obtain 195 g of processed ginseng concentrate powder.

<Example 4: Production of processed red ginseng powder using red ginseng powder>
Add 250 g of carrot powder and 750 g of bran and sterilize with 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 / medium weight g) is inoculated and cultured at 28 ° C. for 7 days. When the culture is complete, 0.02 M sodium acetate buffer is added, mixed and then filtered through the medium. 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% alcohol was added, and the mixture was 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>
Add 250 g of carrot powder and 750 g of bran and sterilize with 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 / medium weight g) is inoculated and cultured at 28 ° C. for 7 days. When the culture is complete, 0.02 M sodium acetate buffer is added, mixed and then filtered through the medium. 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 concentrate 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% alcohol was added, and the mixture was filtered and concentrated to obtain 190 g of processed red ginseng concentrate.

<Example 6: Production of processed red ginseng concentrate powder using red ginseng concentrate powder>
Add 250 g of carrot powder and 750 g of bran and sterilize with a high-pressure steam sterilizer at 121 ° C. and 1.5 atm. 2 L of sterile water is placed in a sterilized medium, mixed, and then inoculated with an Aspergillus niger suspension (5 × 10 ⁵ spores / medium weight g) and cultured at 28 ° C. for 7 days. When the culture is complete, 0.02 M sodium acetate buffer is added, mixed and then filtered through the medium. 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 concentrate 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% alcohol was added, and the mixture was filtered, concentrated and dried to obtain 195 g of processed red ginseng concentrate powder.

The following <Table 1> shows the ginsenoside Rh2 and Rg3 contents 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 enzymes for ginseng powder and red ginseng powder corresponding to Examples 1 to 6 of the present invention, a novel ginsenoside component in which a trace amount was 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 a large amount of Rh2 and Rg3 as compared with the ginseng powder and the red ginseng powder which are the substances to be reacted. In Comparative Examples 7 to 11, Rh2 and Rg3 are simply added to ginseng powder and red ginseng powder which are not treated with saponin-degrading enzyme and organic acid hydrolysis as in the examples of the present invention, and Rh2 as in the examples of the present invention. And Rg3 content, and from now on, it was manufactured to compare the cancer-related fatigue improving effect.

<Experimental Example 1: Effect of Fatigue Improvement Composition Due to Cancer>
The experimental animals were supplied with Balb / c-nu / nu mouse female, which is 6 weeks old and weighs 20 ± 2 g, from 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 the light and darkness were adjusted, and the animals were allowed to freely ingest a feed (Orient Co., Ltd.) for one week, purified, and then macroscopic symptoms were observed. After transplanting 100 μl of HT-29 (5 × 10 ⁶ cells / mouse) cells subcutaneously into the Balb / c nu / nude mice purified for one week, the cells were observed macroscopically. When the tumor size reached 150 mm ³ , mice were randomly grouped and then drug administration was started. The running wheel activity and the swimming test were measured after the administration of the anticancer drug and the drug was completed, and the amount of glycogen synthesized in the muscle homogenized the tissue collected from the thigh on the final autopsy day. After that, the analysis was carried out through the ELISA kit.

-Running wheel activity (Running distance = meter / 10min)
Spontaneous momentum was measured through the Running wheel activity as a parameter of Cancer-related fatigue (CRF). The number of turns rounded for a total of 10 minutes was measured with a wheel of 300φ, 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 hot water (23 ± 1 ° C.) in a transparent constant temperature water tank (500 mm × 500 mm × 400 mm) capable of keeping the temperature and water depth constant, forced swimming (FS) was performed. Immediately after the weakness judgment, the total swimming time was recorded.

-Calculation of rate of increase (%)
Example or Comparative Example Treatment Group Mean-Control Mean x 100
Normal group mean-control average

All Examples, Comparative Examples and the like were diluted with phosphate buffered saline (PBS) according to volume and dispensed, and then forcibly administered orally using an oral administration needle (sonde). The dose was calculated to be 100 mg / kg Body Weight mixed and diluted with PBS at a concentration of 100 mg / kg Body Weight, and 100 μl / 20 g was calculated according to the body weight measured on the day of administration. Was administered in a batch for 4 weeks. The groups for evaluation of this experimental example are as shown in <Table 2>.

For the significance verification of all the following experimental examples, the p-value values were compared at the 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> is the result for Experimental Example 1, and the distance ran for 10 minutes after co-administration of Examples and Comparative Examples in an animal model xenografted with HT-29 colorectal cancer cell line for 4 weeks. The results of the comparative evaluation of the amount of spontaneous exercise due to cancer are shown, and <Table 4> shows the results of the comparative evaluation of the amount of forced exercise due to cancer in the swimming time. After producing saponin-degrading enzyme for ginseng powder and red ginseng powder corresponding to Examples 1 to 6 of the present invention, processed ginseng in which a trace amount of ginsenoside component is increased by using the produced saponin-degrading enzyme and hydrolysis with an organic acid. The powdered or processed ginseng extract showed an increase rate of spontaneous momentum of 62.6 to 96.2% and an increase rate of forced momentum of 63.0 to 98.0%, and the reaction of Examples 1 to 6 of the present invention. It shows the rate of increase in the amount of exercise due to the improvement of cancer-related fatigue, which is superior to the rate of increase in spontaneous exercise and forced exercise of 3.2 to 18.8% shown by the ginseng powder and red ginseng powder of Comparative Examples 1 to 6 corresponding to the target substances. .. Further, the processed ginseng or processed ginseng extract of Examples 1 to 6 of the present invention adds Rh2 and Rg3 to the ginseng powder and red ginseng powder of Comparative Examples 1 and 4, and Rh2 and Rg3 as in Example 1. Cancers having an increase rate of 20.8 to 30.6% in spontaneous momentum and forced momentum due to cancers of Comparative Examples 7 and 8 produced by increasing the Rg3 content to 0.2% by weight and 0.3% by weight, respectively. From the fact that the rate of increase in momentum due to the improvement of related fatigue is shown, it can be seen that the effect of increasing the momentum by improving the cancer-related fatigue of the processed ginseng or the processed ginseng extract of the present invention is increased by the effective components other than Rh2 and Rg3. .. On the other hand, Comparative Examples 9 to 11 are compositions produced by additionally mixing 99 g of red ginseng powder with 1 g of Rh2, 1 g of Rg3, and (0.5 g of Rh2 + 0.5 g of Rg3), respectively, but Comparative Example 9 (Rh2 1). When Comparative Example 11 (Rh2 0.5% by weight + Rg3 0.5% by weight) was administered rather than Comparative Example 10 (containing 1% by weight of Rg3), it showed an excellent therapeutic effect on cancer-related fatigue. It can be confirmed that there is a synergistic cancer-related fatigue improvement or therapeutic effect when these are administered in combination rather than when Rh2 or Rg3 is administered alone.

<Experimental Example 2: Effect of fatigue improving composition by anticancer agent>
The evaluation was carried out under the same conditions as the method of Experimental Example 1, but all the Examples and Comparative Examples were comparatively evaluated under the conditions treated with the anticancer drug. The anti-cancer agent was treated with 5-FU and treated at a concentration of 30 mg / kg three times a week. The groups for evaluation of this experimental example are as shown in <Table 5>.

The following <Table 6> is the result of the above Experimental Example 2. In an animal model in which the HT-29 colorectal cancer cell line was xenografted, the anticancer drug was administered in combination with each Example and Comparative Example for 4 weeks, and then the final autopsy was performed. It is the result of comparing the synthetic amount of Glycogen in the muscle collected from the thigh of the hind leg on a daily basis. As a result, the amount of Glycogen synthesized was reduced by 39.2% in the Xenograft group xenografted with colorectal cancer as compared with the Normal group, and also decreased by 51.4% in the Control group to which the anticancer drug was administered. However, as a result of the combined administration of Examples 1 to 6 together with the anticancer drug treatment, it was confirmed that the amount of glycogen synthesized was significantly increased as compared with the Control group to which the anticancer drug was administered, and it was confirmed that Comparative Example 12 ( In the group to which modafinil) was co-administered, no significant change was observed as compared with the examples. The rate of increase in the amount of glycogen synthesized in each Example and Comparative Example is as shown in <Table 6>.

<Experimental Example 3: Effect of Fatigue Improvement Composition by Radioactivity Treatment>
The evaluation was carried out under the same conditions as the method of Experimental Example 1, but each Example and Comparative Example were comparatively evaluated under the condition of being treated with radiation. Radiation was treated at 10 Gy three times a week. The groups for evaluation of this experimental example are as shown in <Table 7>.

The following <Table 8> is the result of the above-mentioned Experimental Example 3. In an animal model in which the HT-29 colorectal cancer cell line was xenografted, radiation was administered in combination with each Example and Comparative Example for 4 weeks, and then the final necropsy was performed. It is the result of comparing the synthetic amount of Glycogen in the muscle collected from the thigh of the hind leg on a daily basis. As a result, the amount of Glycogen synthesized was reduced by 36.5% in the Xenograft group xenografted with colorectal cancer as compared with the Normal group, and also decreased by 51.4% in the Radiation-treated Control group as compared with the Normal group. However, as a result of the combined administration of Examples 1 to 6 together with the radiation treatment, it was confirmed that the synthetic amount of glycogen was significantly increased as compared with the control group treated with the radiation, and it was confirmed that the synthetic amount of glycogen was increased. In the group to which 4, 7, 9, 10, 11, and 12 (modafinil) were co-administered, no significant change was observed as compared with the examples. The rate of increase in the amount of glycogen synthesized in each Example and Comparative Example is as shown in <Table 8>.

Claims (2)

A pharmaceutical composition for preventing or treating cancer-related fatigue.
The cancer-related fatigue prevention or treatment is due to an increase in spontaneous exercise amount and forced exercise amount.
(A) A step of inoculating Aspergillus niger into a medium composed of carrot powder and bran.
(B) The step of culturing the bacteria of the above step (a),
(C) The step (b) of purifying the culture with an ultrafiltration membrane.
(D) Step (c) Separation of enzyme from purified product,
(E) Ginseng powder, red ginseng powder, ginseng extract, or the step of adding the enzyme to the red ginseng extract, step (d).
(F) The step (e) of fermenting the additive,
(G) The step (f) the step of separating the fermented product,
(H) The step (g) of concentrating the supernatant,
(I) The step of reacting the concentrate with one or more organic acids selected from the group consisting of acetic acid, lactic acid, citric acid, malic acid, and tartaric acid.
(J) Contains the ginseng extract produced in the step (i) of neutralizing and filtering, purifying, concentrating and drying the reactants.
The ginseng extract is a pharmaceutical composition for preventing or treating cancer-related fatigue, which comprises ginsenosides Rh2 and Rg3 in an amount of 1 to 20% by weight, respectively. The cancer-related fatigue is fatigue due to muscle weakness, muscle atrophy, and muscle function damage (cancer cachexia-related fatigue).
The pharmaceutical composition for preventing or treating cancer-related fatigue according to claim 1.