Title:
ANTI-FATIGUE COMPOSITION, FORMULATION AND USE THEREOF
Kind Code:
A1


Abstract:
An anti-fatigue composition consisting of 20(S)-protopanoxadiol and lycium barbarum polysaccharide. Experiments prove that the composition exhibits a significant anti-fatigue effect. In comparison with the effect attained by the single use of lycium barbarum polysaccharide or 20(S)-protopanoxadiol, the combined use of 20(S)-protopanoxadiol and lycium barbarum polysaccharide exerts an obvious a clear synergistic effect.



Inventors:
Xu, Changjiang (Shanghai, CN)
Jia, Weiguo (Shanghai, CN)
Yu, Chunying (Shanghai, CN)
Zhang, Wenjing (Shanghai, CN)
Han, Qiyuan (Shanghai, CN)
Ge, Qiang (Shanghai, CN)
Wang, Qinlin (Shanghai, CN)
Yang, Zirong (Shanghai, CN)
Application Number:
13/812485
Publication Date:
05/16/2013
Filing Date:
07/27/2011
Assignee:
XU CHANGJIANG
JIA WEIGUO
YU CHUNYING
ZHANG WENJING
HAN QIYUAN
GE QIANG
WANG QINLIN
YANG ZIRONG
Primary Class:
International Classes:
A61K31/575; A61K31/715
View Patent Images:



Other References:
Xu et al., CN 101890040 A, 11-2010, machine translation, Retreived on 6/12/2013 from http://worldwide.espacenet.com
Wang et al. Antiprostate cancer effects of 25-OCH3-PPD. British Journal of Cancer (2008) 98(4), 792 - 802
Luo et al. Lycium barbarum Polysaccharides Induce Apoptosis in Human Prostate Cancer Cells and Inhibits Prostate Cancer Growth in a Xenograft Mouse Model of Human Prostate Cancer. J Med Food 12 (4) 2009, 695-703
Li, X. M., Ma, Y. L., & Liu, X. J. (2007). Effect of the Lycium barbarum polysaccharides on age-related oxidative stress in aged mice. Journal of ethnopharmacology, 111(3), 504-511.
Primary Examiner:
MILLER, DALE R
Attorney, Agent or Firm:
MORRISON & FOERSTER LLP (425 MARKET STREET, SAN FRANCISCO, CA, 94105-2482, US)
Claims:
1. An anti-fatigue composition consisting of 20(S)-protopanoxadiol and lycium barbarum polysaccharide.

2. The composition according to claim 1, wherein the weight ratio of the 20(S)-protopanoxadiol and lycium barbarum polysaccharide is 1:50 to 1:1000.

3. A formulation comprising the composition according to claim 1, wherein the formulation consists of 20(S)-protopanoxadiol, lycium barbarum polysaccharide and pharmaceutically acceptable excipients.

4. The formulation according to claim 3, wherein the formulation is in form of tablets, pills, capsules, granules or oral solution.

5. A method for relieving fatigue, comprising administering the composition of claim 1 to a subject.

6. A method for relieving fatigue, comprising administering the formulation of claim 3 to a subject.

7. The method of claim 5, wherein the fatigue results from various causes.

8. The method of claim 7, wherein the fatigue results from diseases.

9. The method of claim 8, wherein the fatigue results from cancer or depression.

10. (canceled)

11. The composition according to claim 1, wherein the weight ratio of the 20(S)-protopanoxadiol and lycium barbarum polysaccharide is 0.01-50 to 60-480.

12. The composition according to claim 11, wherein the weight ratio of the 20(S)-protopanoxadiol and lycium barbarum polysaccharide is 0.01-5 to 120-480.

13. The formulation according to claim 3, wherein the weight ratio of the 20(S)-protopanoxadiol and lycium barbarum polysaccharide is 0.01-50 to 60-480.

14. The formulation according to claim 13, wherein the weight ratio of the 20(S)-protopanoxadiol and lycium barbarum polysaccharide is 0.01-5 to 120-480.

Description:

TECHNICAL FIELD

The present invention belongs to medicine field, particularly relates to an anti-fatigue composition, formulation and use thereof.

BACKGROUND ART

At the fifth International Biochemistry of Exercise Congress in 1982, the fatigue is defined that: the body's physiological processes can not maintain its function at a certain degree or the organs can not maintain its predetermined exercise intensity.

Fatigue is classified as central nervous system fatigue, nerve-muscle joint fatigue and peripheral fatigue of the limbs. Fatigue is a comprehensive physiological process involving many physiological and biochemical factors, and it's a normal physiological phenomenon inevitably occurring at a certain stage of the mental activity or physical activity of the body. It marks a temporary decline of the original work ability of the body, and may be an indication indicating the body develops to an injury status.

At present people are paying more attention to the Chronic Fatigue Syndrome (CFS). CFS is a group of syndrome, which takes long-term durable fatigue as prominent manifestation, accompanying with non-specific manifestations of low fever, headache, sore throat, muscle and joint pain, inattention, memory decline, sleep disorders, depression and the like, generally nothing abnormal is detected in physical examination and routine examination (Holmes G O, Kaplan J E, Gantz N M, et al. Chronic Fatigue Syndrome: A Working Case Definition. Ann Intern Med, 1988, 108(3): 387-389; Fukuda K, Straus S E, Hickie I, et al. The Chronic Fatigue Syndrome: A Comprehensive Approach to Definition and Study. Ann Intern Med, 1994, 121(12): 953-959). CFS is more likely to happen in people at the age group of 20-50 years old, and more common in women. CFS significantly affects work and living of a subject and gains great concern in the medical field.

There are many causes which may lead to fatigue, such as working environment, diet habit and lifestyle, especially the diseases, which may bring to a subject mental stress, physical exertion, and lowered resistance in various functions of the body; as well as the physical exertion caused by drugs, which is easy to lead to fatigue. For example, the symptom of fatigue is normally seen in a cancer or mental patient who is subjected to a treatment.

Currently, the widely used methods of relieving fatigue adjust the body function by sleep and recuperation etc. On the other hand, the body function can be improved by recuperating with external materials. However, there is no anti-fatigue medicament or food with significant effect available in the current market.

Lycium chinense, which is ripe fruit of a deciduous small shrub of Lycium plants in Solanaceae family, is a traditional Chinese herb medicine having effects of strengthening with tonics, replenishing vital essence, dispelling rheumatism, invigorating Yang, strengthening muscles and bones etc. It is recorded in an ancient Chinese medical book named Dietetic Materia Medica that, ripe fruits of Lycium chinense have the functions of “strengthening muscles to endure hard work, dispelling rheumatism, nourishing and benefiting muscles and bones, benefiting human body, and removing asthenic disease”. Research of modern pharmacology proves that, the active ingredient of Lycium chinense fruits is lycium barbarum polysaccharide which has the functions of reducing the level of blood sugar and blood fat, improving immunity, antioxidation and anti-fatigue etc. At present, there are literatures reporting the anti-fatigue effect of Lycium chinense fruits as follows:

LUO Qiong et al. reports the influence of lycium barbarum polysaccharide on the anti-fatigue effect of mice, experiments show that lycium barbarum polysaccharide is the main ingredient for anti-fatigue effect of Lycium chinense fruits (LUO Qiong, YAN Jun and ZHANG Shenghua. Influence of Lycium Barbarum Polysaccharide on the Anti-fatigue Effect for Mice. Journal of Hubei Medical University, 1999, No. 4); WANG Yanwu et al. reports that lycium barbarum polysaccharide has anti-fatigue effect (WANG Yanwu, FU Weizhong, TAN Zongyan et al. Experimental Research on Anti-fatigue Effect of Lycium Barbarum Polysaccharide. China Tropical Medicine, 2006, No. 8, August 2006,(6):8); PAN Jingyi et al. reports that Lycium chinense fruits has functions of anti-fatigue, improving exercise tolerance and immunity for mice (Experimental Research on Anti-fatigue and Improving Immunity Effects of Lycium chinense Fruits, Shanghai Journal of Preventive Medicine, 2003, Vol. 15, No. 8).

Protopanoxadiol is aglycon of ginsenoside diol set, including 20(S)-protopanoxadiol and 20(R)-protopanoxadiol, which are enantiomers to each other and are represented by the following formulas.

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20(S)-protopanoxadiol, which does not occur naturally, is a metabolite of ginsenoside in the body. Chinese Patent Application No. CN200610027507.1 discloses the anti-depression activity of 20(S)-protopanoxadiol; Chinese Patent Application No. CN200610027508.6 discloses the anti-intestinal cancer activity of 20(S)-protopanoxadiol; Chinese Patent Application No. CN200610131959.4 discloses novel use of ginsenoside Rh2 for anti-fatigue; Chinese Patent Application No. CN200610017063.3 discloses anti-fatigue effect of a composition comprising ginseng, coffee and tea. The single use of 20(S)-protopanoxadiol for anti-fatigue has not been reported yet.

Although lycium barbarum polysaccharide has a certain anti-fatigue effect, such effect needs to be improved. Until now, there is no patent or literature reporting using 20(S)-protopanoxadiol and lycium barbarum polysaccharide for anti-fatigue.

CONTENTS OF THE INVENTION

The object of the invention is to provide an anti-fatigue composition. Another object of the invention is to provide a formulation comprising the composition.

Still another object of the invention is to provide use of the composition.

The anti-fatigue composition according to the invention consists of 20(S)-protopanoxadiol and lycium barbarum polysaccharide.

In the composition, the weight ratio of the 20(S)-protopanoxadiol and lycium barbarum polysaccharide is 0.01-50 to 60-480.

Preferably in the composition, the weight ratio of the 20(S)-protopanoxadiol and lycium barbarum polysaccharide is 0.01-5 to 120-480.

The invention also provides a formulation comprising the above composition, wherein the formulation consists of the composition and pharmaceutically acceptable excipient, and the formulation may be in form of tablets, pills, capsules, granules or oral solution.

The pharmaceutically acceptable excipient is one or more selected from the group consisting of filler, disintegrating agent, adhesive, lubricant, diluent, sweetener, flavoring agent, coloring agent, emulsifier and suspending agent.

The filler is one or more selected from the group consisting of lactose, sucrose, dextrin, mannitol, sorbitol, microcrystalline cellulose and starch.

The disintegrating agent is selected from the group consisting of microcrystalline cellulose, starch, low substituted hydroxypropyl cellulose and crosslinked polyvinylpyrrolidone.

The adhesive is selected from the group consisting of polyvinylpyrrolidone, starch and ethanol.

The lubricant is selected from the group consisting of magnesium stearate, sodium lauryl sulfate, silica and talc.

The diluent is selected from the group consisting of water, ethanol, propylene glycol and glycerol.

The sweetener is one or more selected from the group consisting of glucose, fructose, sucrose, maltose, starch sugar and lactose.

The instant invention further provides use of the above composition and formulation thereof in the preparation of medicaments and healthcare products for anti-fatigue.

The fatigue may result from various causes.

Preferably the fatigue results from diseases.

More preferably the fatigue results from cancer or depression.

Experiments show that the composition according to the invention which consists of 20(S)-protopanoxadiol and lycium barbarum polysaccharide has a synergistic effect in anti-fatigue.

SPECIFIC MODE FOR CARRYING OUT THE INVENTION

The following Examples are intended to further illustrate the present invention without limiting its scope.

Experimental Example 1

Effect of Composition Consisting of 20(S)-protopanoxadiol and Lycium barbarum Polysaccharide on Mice Burden Swimming Time

According to the Technical Standards for Testing & Assessment of Health Food issued by the Ministry of Health, P. R. China, function and biochemistry indexes assessment of the mixture of 20(S)-protopanoxadiol and lycium barbarum polysaccharide on the function of relieving physical fatigue is conducted; the detailed method is given as follows:

1. Experimental animals: ICR mice, male, 18-22g, provided by Shanghai Slack laboratory animal Co. Ltd., license number: SCXK (Shanghai) 2007-0005;

2. Experimental drugs:

20(S)-protopanoxadiol: provide by Shanghai Innovative Research Center of Traditional Chinese Medicine, batch number: 20050606-1, purity: 94%; lycium barbarum polysaccharide: provided by Shanghai KangZhou Fungi Extract Co. Ltd., polysaccharide content≧30%.

To 20(S)-protopanoxadiol is added a small amount of 0.3% CMC-Na, followed by grinding to form a suspension and diluting with CMC-Na to a desired concentration. Then lycium barbarum polysaccharide is added to the 20(S)-protopanoxadiol suspension to form a composition with a certain concentration.

3. Experimental groups: the mice are randomly divided into 19 groups by weight, 20 mice per each group; the detailed groups are as follows:

normal (solvent) control

20(S)-protopanoxadiol: 0.01 mg/kg

20(S)-protopanoxadiol: 0.5 mg/kg

20(S)-protopanoxadiol: 1 mg/kg

lycium barbarum polysaccharide: 120 mg/kg

lycium barbarum polysaccharide: 240 mg/kg

lycium barbarum polysaccharide: 480 mg/kg

20(S)-protopanoxadiol+lycium barbarum polysaccharide: 0.01 mg/kg+120 mg/kg

20(S)-protopanoxadiol+lycium barbarum polysaccharide: 0.01 mg/kg+240 mg/kg

20(S)-protopanoxadiol+lycium barbarum polysaccharide: 0.01 mg/kg+480 mg/kg

20(S)-protopanoxadiol+lycium barbarum polysaccharide: 0.5 mg/kg+120 mg/kg

20(S)-protopanoxadiol+lycium barbarum polysaccharide: 0.5 mg/kg+240 mg/kg

20(S)-protopanoxadiol+lycium barbarum polysaccharide: 0.5 mg/kg+480 mg/kg

20(S)-protopanoxadiol+lycium barbarum polysaccharide: 1 mg/kg+120 mg/kg

20(S)-protopanoxadiol+lycium barbarum polysaccharide: 1 mg/kg+240 mg/kg

20(S)-protopanoxadiol+lycium barbarum polysaccharide: 1 mg/kg+480 mg/kg

20(S)-protopanoxadiol+lycium barbarum polysaccharide: 5 mg/kg+120 mg/kg

20(S)-protopanoxadiol+lycium barbarum polysaccharide: 5 mg/kg+240 mg/kg

20(S)-protopanoxadiol+lycium barbarum polysaccharide: 5 mg/kg+480 mg/kg

4. Experimental method:

0.2ml/10 g of drug is administrated by gavage every day; for normal control group, 0.2 ml/10 g of distilled water is administrated by gavage every day; once a day, 30 days in total.

30 minutes after the last time of administrating drug, the end of the tail of each mouse is loaded with copper wires corresponding to 6% of its body weight, then the mouse is put in a swimming box to swim, the time from start of swimming to death of the mouse is recorded, i.e. the mice burden swimming time; the water depth in the swimming box is 30cm or more, and water temperature is 23+1.0° C.

5. Statistical data processing: t-test is conducted to calculate P value, Jin Zhengjun formula is used to conduct combined medication analysis.

6. Experimental results:

Mice burden swimming test is conducted with drug dosages of 0.01-5 mg/kg of 20(S)-protopanoxadiol and 120-480 mg/kg of lycium barbarum polysaccharide, the results are shown in Table 1:

TABLE 1
Effect of 20(S)-protopanoxadiol and lycium barbarum polysaccharide on
mice burden swimming time ( x ± S)
AnimalChange rate
DosageAnimalweightSwimmingof swimming
Groups(mg/kg) numberstart/finish (g)time (s) time (%)
normal control groupsolvent2021.7/39.3620 ± 285
20(S)-protopanoxadiol0.012021.6/39.2640 ± 275 1.5
20(S)-protopanoxadiol0.52021.8/38.8660 ± 268 1.9
20(S)-protopanoxadiol12021.7/38.7658 ± 296 2.2
20(S)-protopanoxadiol52021.8/38.9640 ± 286 1.5
lycium barbarum1202021.7/39.5 783 ± 189**26.4
polysaccharide
lycium barbarum2402021.8/39.7 794 ± 385**28.1
polysaccharide
lycium barbarum4802021.8/38.8766 ± 282* 23.5
polysaccharide
20(S)-protopanoxadiol + lycium0.01 + 120 2021.7/39.5798 ± 235**28
barbarum polysaccharide
20(S)-protopanoxadiol + lycium0.01 + 240 2021.8/39.2 843 ± 283** 40
barbarum polysaccharide
20(S)-protopanoxadiol + lycium0.01 + 480 2021.9/38.8 865 ± 298** 42.6
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 0.5 + 120 2021.8/39.3853 ± 229** 35.5
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 0.5 + 240 2021.8/39.1898 ± 322** 44.8
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 0.5 + 480 2021.8/38.7 923 ± 224** 48.9
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 1 + 1202021.8/39.4842 ± 252** 35.78
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 1 + 2402021.9/39.1993 ± 289**60.2
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 1 + 4802021.8/38.3 1063 ± 342** 71.4
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 5 + 1202021.7/39.2875 ± 279** 36.42
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 5 + 2402021.9/38.81069 ± 243** 62.8
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 5 + 4802021.8/39.0 1185 ± 242** 75.1
barbarum polysaccharide
Note:
compared with normal control group,
*P < 0.05,
**P < 0.01

The results in Table 1 show that: as compared with normal group, lycium barbarum polysaccharide can prolong the mice burden swimming time at different levels, the composition consisting of 20(S)-protopanoxadiol and lycium barbarum polysaccharide in a weight ratio of 0.01-5 to 120-480 can prolong the mice burden swimming time at different levels (P<0.01, P<0.05); as compared with the effect of 20(S)-protopanoxadiol or lycium barbarum polysaccharide, the composition consisting of 20(S)-protopanoxadiol and lycium barbarum polysaccharide in a weight ratio of 0.01-5 to 120-480 can also prolong the mice burden swimming time at different levels (P<0.01, P<0.05).

Conclusion: combined use of 20(S)-protopanoxadiol and lycium barbarum polysaccharide exerts an obvious synergistic effect.

Experimental Example 2

Effects of the Combined Dosage of 20(S)-protopanoxadiol and Lycium barbarum Polysaccharide on Mice Burden Swimming Time

Other than the combined dosage of Experimental example 1, the range of combined dosage is enlarged to conduct multi-batch experiments. The experimental animals, drugs and method are the same as those of Experimental example 1, and the final results are shown in Table 2:

TABLE 2
Effect of 20(S)-protopanoxadiol and lycium barbarum polysaccharide on
mice burden swimming time
Swimming time
Dosage change rate
Groups(mg/kg)(%)
normal control groupsolvent0 
20(S)-protopanoxadiol0.011.5
20(S)-protopanoxadiol0.51.9
20(S)-protopanoxadiol12.2
20(S)-protopanoxadiol31.6
20(S)-protopanoxadiol6.251.4
20(S)-protopanoxadiol12.53.4
20(S)-protopanoxadiol256.9
20(S)-protopanoxadiol5012.4*
lycium barbarum polysaccharide107.5
lycium barbarum polysaccharide308.1
lycium barbarum polysaccharide6010.5 
lycium barbarum polysaccharide120 26.4**
lycium barbarum polysaccharide240 28.1**
lycium barbarum polysaccharide48023.5*
20(S)-protopanoxadiol + lycium0.01 + 60  21.3*
barbarum polysaccharide
20(S)-protopanoxadiol + lycium0.01 + 120   28**
barbarum polysaccharide
20(S)-protopanoxadiol + lycium0.01 + 240   40**
barbarum polysaccharide
20(S)-protopanoxadiol + lycium0.01 + 480 42.6**
barbarum polysaccharide
20(S)-protopanoxadiol + lycium0.5 + 60 25.5**
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 0.5 + 120 35.5**
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 0.5 + 240 44.8**
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 0.5 + 480 48.9**
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 1 + 6022.6* 
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 1 + 12035.78** 
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 1 + 24060.2**
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 1 + 48071.4**
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 3 + 6022.8* 
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 3 + 12036.8**
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 3 + 24038.7**
barbarum polysaccharide
20(S)-protopanoxadiol + lycium6.25 + 60  17.6* 
barbarum polysaccharide
20(S)-protopanoxadiol + lycium6.25 + 120 22.5* 
barbarum polysaccharide
20(S)-protopanoxadiol + lycium6.25 + 240 32.9**
barbarum polysaccharide
20(S)-protopanoxadiol + lycium12.5 + 120 26.6**
barbarum polysaccharide
20(S)-protopanoxadiol + lycium25 + 6038.1**
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 25 + 12041.7**
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 25 + 24050.1**
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 25 + 48032.9**
barbarum polysaccharide
20(S)-protopanoxadiol + lycium50 + 6041.9**
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 50 + 12042.8**
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 50 + 24048.1**
barbarum polysaccharide
20(S)-protopanoxadiol + lycium 50 + 48055.5**
barbarum polysaccharide
Note:
compared with normal control group,
*P < 0.05,
**P < 0.01

The results in Table 2 show that: as compared with normal control group, single use of 20(S)-protopanoxadiol has no significant effect on mice swimming time (P>0.05), use of 120-480 mg/kg of lycium barbarum polysaccharide alone can prolong mice swimming time at different levels (P<0.05, P<0.01), the composition of 20(S)-protopanoxadiol and lycium barbarum polysaccharide in a weight ratio of 0.01-50 to 60-480 can apparently prolong mice burden swimming time (P<0.01 or P<0.05); as compared with the effect of use of 20(S)-protopanoxadiol or lycium barbarum polysaccharide alone, the effect of combined use of 20(S)-protopanoxadiol and lycium barbarum polysaccharide on mice burden swimming time is bigger than the sum of the effects of single use of the two, that is to say, although 20(S)-protopanoxadiol has no effect on mice burden swimming endurance, combined use of 20(S)-protopanoxadiol and lycium barbarum polysaccharide exerts apparent and unexpected synergistic effect.

Conclusion: combined use of 20(S)-protopanoxadiol and lycium barbarum polysaccharide exerts apparent synergistic effect.

Example 1

Tablets of the Anti-Fatigue Composition

500 g of lactose is added to 4 g of 20(S)-protopanoxadiol and 2000 g of lycium barbarum polysaccharide, followed by mixing uniformly, taking 70% ethanol as adhesive, granulating, drying, and then adding 10 g of magnesium stearate and tabletting to obtain tablets.

Example 2

Capsules of the Anti-Fatigue Composition

200 g of lactose is added to 8 g of 20(S)-protopanoxadiol and 2000 g of lycium barbarum polysaccharide, followed by mixing uniformly, taking 70% ethanol as adhesive, granulating and filling in capsule to obtain the capsules.

Example 3

Oral Solution of the Anti-Fatigue Composition

100 g of Tween-80 is added to 16 g of 20(S)-protopanoxadiol and 2000 g of lycium barbarum polysaccharide, followed by grinding to form primary emulsion, adding water to a volume of 5000 ml to obtain the oral solution.

INDUSTRIAL APPLICABILITY

The anti-fatigue composition according to the invention consists of 20(S)-protopanoxadiol and lycium barbarum polysaccharide. The experiments show that the composition can apparently prolong the swimming time of mice with weight loading, i.e. it exerts an obvious synergistic effect in anti-fatigue. In comparison with the effect attained by the single use oflycium barbarum polysaccharide or 20(S)-protopanoxadiol, the combined use of 20(S)-protopanoxadiol and lycium barbarum polysaccharide exerts an obvious synergistic effect. The composition according to the invention can be used in the preparation of anti-fatigue medicaments and healthcare products; it provides a novel method of relieving fatigue and possesses industrial applicability.