ANTI-FATIGUE COMPOSITION AND USE THEREOF
20180333427 ยท 2018-11-22
Assignee
- CHENGZHI LIFE SCIENCE., LTD. (Jiangxi, CN)
- CHENGZHI LIFE SCIENCE CORPORATION (Beijing, CN)
- Bioenergy Life Science, Inc. (Ham Lake, MN, US)
Inventors
Cpc classification
A23V2002/00
HUMAN NECESSITIES
A23V2200/31
HUMAN NECESSITIES
A23L33/105
HUMAN NECESSITIES
A23V2002/00
HUMAN NECESSITIES
A23V2200/31
HUMAN NECESSITIES
A61P43/00
HUMAN NECESSITIES
A23G3/36
HUMAN NECESSITIES
A23G3/48
HUMAN NECESSITIES
A23G3/42
HUMAN NECESSITIES
A61K2300/00
HUMAN NECESSITIES
A61K2300/00
HUMAN NECESSITIES
International classification
A61K31/7004
HUMAN NECESSITIES
A61K31/522
HUMAN NECESSITIES
A23L33/105
HUMAN NECESSITIES
Abstract
Disclosed is a composition with a sustainable anti-fatigue function and which helps the body to restore the level of high-energy phosphate materials and increases energy, wherein the active ingredients thereof are ribose and caffeine. The composition comprises components with the following weight parts: 1-99.9 parts ribose and 0.1-99 parts coffee or 1-99.99 parts ribose and 0.01-99 parts caffeine.
Claims
1. A method of treating fatigue in a subject in need thereof comprising administering a composition of ribose and caffeine as effective ingredients to the subject in an effective amount to sustain an anti-fatigue effect and help the subject's body restore high-energy phosphate substances to increase energy, wherein the composition comprises caffeine to ribose in a weight ratio of 12.5 to 100.
2. The method according to claim 1, wherein the composition further comprises at least one of milk powder or fresh milk, amino acids, sugars, sugar alcohols, cereals, cocoa, chocolate, non-saccharide and sugar alcohols sweeteners, pectin, soluble dietary fibers, salts, other carbohydrates, vitamins, minerals, carbon dioxide or other food additives; wherein, the amino acids comprise one or more of taurine, pyruvic acid, ketoglutaric acid, arginine and citrulline; the sugars comprise one or more of glucose, sucrose or fructose; the non-saccharide and sugar alcohols sweeteners comprise one or more of stevia, aspartame, sucralose, Momordica grosvenori, glycyrrhizin, beet sweetener or saccharin sodium; the sugar alcohols comprise one or more of xylitol, erythritol, maltitol, isomalt or sorbitol; wherein the minerals comprise one or more elements of calcium, magnesium, iron and zinc; the salts comprise one or more salts of sodium, potassium and phosphate; said other carbohydrates comprise wheat flour, inulin, oligosaccharides, starch and/or soluble or insoluble dietary fibers; said wherein other food additives comprise one or more of essences, colorants, malic acid, citric acid, sodium citrate, sorbic acid, potassium sorbate, benzoic acid, sodium benzoate, edible gum base, sucrose esters, soy lecithin and sodium alginate; the essences and colorants are synthetic or natural; and the caffeine is derived from cocoa, coffee, guarana, tea or chocolate.
3. The method according to claim 2, wherein the composition comprises 0.1-60 ribose, 0.01-100 coffee or aqueous extracts of coffee and 0.01-10 milk powder or fresh milk by weight.
4. The method according to claim 2, wherein the composition comprises 0.01-20% milk powder or fresh milk.
5. The method according to claim 2, wherein the composition comprises 0.01-20% amino acids.
6. The method according to claim 2, wherein the composition comprises 0.1-60 ribose, 0.01-100 coffee or aqueous extracts of coffee, 0-20 milk powder or fresh milk, 0-10 cocoa, 0.01-60 sugars, 0-15 sugar alcohols, 0-5 non-saccharide and sugar alcohols sweeteners, 0-10 pectin, 0-60 soluble dietary fiber, 0-60 other carbohydrates, 0-0.5 vitamins, 0-5 essence, 0-50 edible gum base and/or 40-99 water by weight.
7. The method according to claim 2, wherein the composition further comprises 0.01-60% sugars, 0-5% non-saccharide sweeteners, 0-20% soluble dietary fibers, 0-0.5% vitamins, 0-10% citric acid, 0-2% sodium citrate, 0-3% sorbic acid or potassium sorbate, 0-2% benzoic acid or sodium benzoate, 0-5% carbon dioxide, 0-5% colorants, 0-5% essences and 1-99% water by weight.
9. The method according to claim 3, wherein the composition further comprises 0-5% minerals, 0-60% sugars, 0-5% non-saccharide sweeteners, 0-20% soluble dietary fibers, 0-10% citric acid, 0-3% sorbic acid or potassium sorbate, 0-2% benzoic acid or sodium benzoate, 0-0.5% carbon dioxide, 0-5% colorants, 0-5% essences and/or 50-99% water by weight.
10. The method according to claim 1, wherein the composition comprises: ribose 0.25 g/kg and caffeine 5 mg/kg; ribose 0.25 g/kg and caffeine 20 mg/kg; ribose 0.5 g/kg and caffeine 5 mg/kg; ribose 0.5 g/kg and caffeine 10 mg/kg; or ribose 0.5 g/kg and caffeine 20 mg/kg.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0033]
[0034]
[0035]
[0036]
DETAILED DESCRIPTION OF THE INVENTION
[0037] The following examples are used for illustrating the present invention but not intended to limit the scope of the present invention. Unless otherwise specified, the techniques used in the examples are conventional technical means known to those skilled in the art, and the materials used are commercially available.
EXAMPLE 1
Anti-Fatigue Test of Ribose Combined with Caffeine
1. Establishment of Fatigue Mouse Models
1.1 Experimental Animal Source
[0038] Experimental animals are ICR male mice with weight of 18-20 g, which are purchased from Beijing Vital River Laboratory Animal Technology Co., certificate of conformity No.: SCXK (Beijing) 2012-0001.
1.2 Weight Loading Swimming Test of Mice
[0039] A lead wire with a weight equivalent to 7.5% body weight of each mouse is fixed to the tail of the corresponding mouse, and the mice are placed into 30 cm25 cm25 cm water tanks with water tempreture of 30 C. and water depth of 20 cm, with two mice per tank. The mice are made swim until the mice are fatigued (submerging in water for 4 seconds), after rest for 20 minutes, then the mice are made swim again until the mice are fatigued, and the times of the two swimming are respectively recorded. The mice swim with the load twice every day, respectively in the morning and afternoon. The sum of the swimming times is recorded as the swimming time for one day. The average of the swimming times for the last two days is taken as a reference, and the mice are kept swimming every day until the day in which the swimming time is below 80% of the reference, and that is considered as fatigue.
1.3 Grouping and Administration
[0040] The mice which have been identified as fatigue are divided again into five groups, i.e. model group, control group (glucose 1 g/kg), ribose group (ribose 2.5 g/kg), caffeine group (caffeine 75 mg/kg), and ribose plus caffeine group (ribose 1250 mg/kg+caffeine 40 mg/kg), by counterpoint grouping method. The respective agents are given by intragastric administration with a dosage of 0.2 ml/10 g, and the daily dose is given in three times. The mice are administrated with the agents 30 minutes before swimming in the morning and afternoon, respectively, and administrated again when the furs of the mice dry after swimming in the afternoon. The mice are continued to swim for three days under the prior condition as described in Section 1.2. After swimming, the respective agents are continually administered to the mice 3 times/day for 3 days, except those to be sampled immediately, then taken as materials.
1.4 Experimental Results
[0041]
[0042] The results show that after supplementation of glucose, ribose, caffeine, and ribose plus caffeine to the fatigue mice, the swimming time for caffeine group mice is shortened with the extension of training time, therefore, caffeine does not produce sustained anti-fatigue effect. The swimming time for ribose group and ribose plus caffeine group is increased with the extension of training time, namely, the anti-fatigue effect for ribose plus caffeine group is better than that for caffeine alone, and ribose plus caffeine group produces a more significant effect.
[0043] Ribose has anti-fatigue effect, as well as caffeine, but they have different action mechanisms and can be complementary with each other. Further studies on anti-fatigue effect of the composition have not been reported yet. The composition containing ribose and caffeine of the present invention may provide a more sustainable and effective anti-fatigue product and has an anti-fatigue effect of real significance.
[0044] In the state of fatigue, the administration of ribose can restore energy more quickly than the control group (i.e. glucose). The administration of caffeine alone can restore some strength in a short time but increase fatigue with the extension of time. The composition containing ribose and caffeine of the present invention can not only achieve anti-fatigue effect in a short time, but also extend the duration time of anti-fatigue effect, hence it has better anti-fatigue effect compared to caffeine.
EXAMPLE 2
Ratio Study About Ribose Combined with Caffeine
1. Experimental Animals
[0045] Experiment animals are ICR male mice with the weight of 18-20 g, which are provided by Beijing Vital River Laboratory Animal Technology Co., certificate of conformity for: SCXK (Beijing) 2012-0001.
2. Drugs and Reagents
[0046] D-Ribose: provided by Chengzhi Life Science and Technology Co. Ltd., batch number: 20121112.
[0047] Caffeine: provided by Chengzhi Life Science and Technology Co. Ltd.
[0048] Positive drug: CAO Kaiyong nutrient solution for men, purchased from Tianjin Kay Yong Health Products Co. Ltd., batch number: 113002. The dosage for oral administration by the human is 10 ml/piece, three pieces every day, namely 0.5 ml/kg calculated based on a body weight of 60 kg, and the dosage for the tested mice is 10 times the dosage for human, namely 5 ml/kg for mice.
3. Experimental Methods
3.1 Preparation of Fatigue Models
[0049] A lead wire with a weight equivalent to 5% body weight of each mouse is fixed to the tail of the corresponding mouse, and the mice are placed into 40 cm50 cm25 cm water tanks with water tempreture of 30-33 C. and water depth of 20 cm, with ten mice per tank. The mice are made swim until the mice are fatigued (submerging in water for 3 seconds). After rest for 20 minutes, the mice swim again until the mice are fatigued. After rest 20 minutes again, the above steps are repeated. The sum of swimming time within two hours is recorded. The experimental process in the morning is performed again in the afternoon. The sum of swimming time in one day is calculated as a basis for grouping.
3.2 Selection of Respective Factor Levels and Administration for Each Group
[0050] Considering literature, routine application situation and pre-test results, D-ribose doses administered to the mice are 0.25 g, 0.5 g, 1 g/kg; and caffeine dose administered to the mice are 5 mg, 10 mg, 20 mg/kg. According to the requirements of the experimental purpose, two factors for respective three levels are selected. D-ribose groups with dosages of 0.25 g, 0.5 g, 1 g/kg, caffeine groups with dosages of 5 mg, 10 mg, 20 mg/kg, and Cao Kaiyong nutrient solution groups using as control groups are set separately, 17 experimental groups are included in the present experiment in total. The corresponding agents are given by intragastric administration for three days, with a daily dose in twice and the time of administration at 10 a.m. and 10 p.m. every day. On day 4, a daily dose of each agent is given by intragastric administration once, 30 minutes after administration, a lead wire with a weight equivalent to 5% body weight of each mouse is fixed to the tail of the mouse, with the same condition as mentioned above, and the mice swim until the mice is dead. The swimming time is recorded, and the averages for each group are calculated and compared between groups.
TABLE-US-00001 TABLE 1 Factor-level table factors levels A D-ribose (g/kg) B caffeine (mg/kg) 1 0.25 5 2 0.5 10 3 1 20
4. Analysis Method
[0051] The average time of swimming until death for each group is calculated as a basis for data analysis, the average time for each group is compared with that for the control group and analyzed (
EXAMPLE 3
Effects of Ribose and Caffeine on Recovery of High-Energy Phosphate Substances in Gastrocnemii of Fatigue Mice
1. Establishment of Fatigue Models
[0052] A lead wire with a weight equivalent to 5% body weight of each mouse is fixed to the tail of the corresponding mouse, and the mice are placed into 40 cm50 cm25 cm water tanks with water tempreture of 30-33 C. and water depth of 20 cm, with ten mice per tank. The mice swim until the mice are fatigued (submerging in waterd for 3 seconds). After rest for 20 minutes, the mice swim again until the mice are fatigued. After rest for 20 minutes again, the above steps are repeated. Each swimming time is recorded separately until the sum of the swimming time is up to 2 hours. The experimental process in the morning is performed again in the afternoon until the sum of the swimming time is up to 2 hours.
2. Grouping and Administration
[0053] After modeling, the gastrocnemii of 10 fatigued mice and 10 normal mice, i.e. fatigue group and normal control group, are immediately taken. The rest of the mice are randomly divided into six groups according to the swimming time on day 1, namely Cao Kaiyong group, model group, and the groups of D-ribose 1 g+caffeine 20 mg/kg, the group of D-ribose 0.5 g+caffeine 10 mg/kg, the group of D-ribose 0.25 g+caffeine 5 mg/kg and the group of caffeine 20 mg/kg, with the administration volume of 10 ml/kg. After modeling, the intragastric administration is performed once daily for three days, 30 minutes after the last administration, the gastrocnemii are taken as materials as stated above, and the contents of ATP, ADP, AMP and IMP in the gastrocnemii are measured by high performance liquid chromatography.
3. Taking and Processing of the Gastrocnemii
[0054] The gastrocnemii are taken from the fatigue mice and the muscle tissue samples are placed in a freezer in 80 C. and dried overnight. After weighing with a electronic scale having the sensitivity of 0.0001 g, the samples are immediately placed into precooled glass grinder, with 0.4 mol/L perchloric acid solution precooled at 4 C. being added according to the solvent volume to the tissue weight ratio of 10 ml/g, then quickly ground into skeletal muscle homogenates in an ice bath, mixed in a vortex for 2.0 minutes, and centrifuged at 4 C. (4000 r/min) for 15 minutes, and the supernatant is taken. The pH of the supernatant is adjusted to 6.5 with 1.0 mol/L sodium hydroxide solution precooled at 4 C., centrifuged again at 4 C. (4000 r/min) for 15 minutes, the supernatant is taken and filtered through 0.2 m microfiltration membrane to obtain skeletal muscle extracts, i.e. test solutions, which are stored in 80 C. for test.
4. Results
[0055] The results show that in the gastrocnemii of the fatigue mice after weight loading swim, the contents of high-energy phosphate substances such as ATP, ADP, AMP, etc. are decreased, while the metabolite IMP of high-energy phosphate substances is significantly increased (compared with the control group, P<0.01). After taking a rest for 2 days, the mice of the model group have restored some the high-energy phosphate substances in the gastrocnemii. After D-ribose plus caffeine is used, ATP content in the gastrocnemii of the middle- and high-dose groups are significantly increased (compared with the model group, P<0.05, P<0.01). The middle- and low-dose groups of D-ribose plus caffeine also enable ADP content in the gastrocnemii of mice to be significantly increased (compared with the model group, P<0.05, P<0.01). Experimental results are shown in
EXAMPLE 4
Ribose Plus Coffee and the Preparation Thereof
[0056] The ribose plus coffee are prepared by adding ribose into instant coffee or triad coffee, with 0.01-5.0 g ribose for one portion of coffee or triad coffee, and mixing evenly. For example, the ribose plus coffee can be obtained by mixing ribose 25 g with 36 g instant coffee evenly.
EXAMPLE 5
Beverage Containing Ribose and Coffee
[0057] The formula of the beverage is that: ribose 18 g, milk powder 14 g, instant coffee 20 g, white granulated sugar 32 g, cocoa 3.9 g, stevia 0.2 g, pectin 5.4 g, soluble dietary fibers 13.8 g, vitamin C 0.5 g, essences 0.006 g and water 1000 mL.
EXAMPLE 6
Food Containing Ribose and Caffeine
[0058] 1. A Beverage Containing Ribose and Caffeine may be Obtained by Adding 0.01-10.0% of Ribose into Beverage Containing Caffeine. Examples are Given as Follows
[0059] Formula I: ribose 8 g, caffeine 15 mg or guarana extract 200 mg (containing 10% caffeine), skimmed milk powder 20 g, white granulated sugar 18 g, fructose 5 g, vitamin C 0.6 g, aspartame 0.2 g, cyclamate 0.05 g, soluble dietary fibers 14 g, citric acid 0.9 g, sodium citrate 0.1 g, sodium benzoate 0.35 g, caramel colorant 0.06 g, vanillin 30 mg, sucrose ester 0.5 g and water 1000 mL.
[0060] Formula II: ribose 10 g, caffeine 300 mg, taurine 4 g, magnesium chloride 0.2 g, vitamins (C, B2, niacinamide, calcium pantothenate) 0.1 g, white granulated sugar 5 g, sucralose 0.05 g, soluble dietary fibers 16 g, citric acid 1.2 g, potassium sorbate 0.3 g, food colorants 0.001 g, apple essence 0.01 g, carbon dioxide 4.8 g and water 1000 mL.
[0061] Formula III: refreshing beverage containing ribose plus coconut and preparation thereof
[0062] White granulated sugar is cooked in water in a jacketed kettle to form concentrated syrup with a concentration of 50%, then filtered through filter separator for use. Coconut milk is added into a mixing tank, after being diluted to a certain volume, blended with 10% filtered coconut milk, then added with citric acid solution to adjust pH to 6-7, added with 18% concentrated syrup, 1% ribose, 0.05% table salt, 0.2% emulsifier (monoglyceride), and an appropriate amount of stabilizer (xanthan gum), heated to 80 C., after high pressure homogenization, sterilized at 121 C. for 15 minutes and canned.
[0063] 2. Food of Energy Bars (Gum) Containing Ribose and Caffeine
[0064] Formula IV: ribose 3 g, caffeine 50 mg, taurine 2 g, vitamins (C, B2, niacinamide, calcium pantothenate) 0.1 g, white sugar 12 g, fructo-oligosaccharide 16 g, cocoa powder 8 g, cocoa butter 15 g, glucose syrup 5 g, peanut butter 5 g, soy protein 10 g, wheat flour 20 g, oat 5 g, emulsifier 0.2 g, essences 0.1 g and an appropriate amount of water.
[0065] Formula V: ribose 3 g, caffeine 30 mg, vitamins (C, E) 0.1 g, white sugar 12 g, fructo-oligosaccharide 5 g, dietary fibers 15 g, glucose syrup 5 g, tragacanth 3 g, apple juice concentrate 1 g, emulsifier 0.2 g, essences 0.1 g, sodium chloride 0.1 g, potassium chloride 0.08 g, honey 1 g and an appropriate amount of water.
[0066] Formula VI: ribose 3 g, caffeine 40 mg, branched-chain amino acids 1 g, white sugar 10 g, cocoa butter 24 g, cocoa powder 16 g, milk powder 5 g, glucose syrup 15 g, inulin 10 g, soy lecithin 0.2 g and essences 0.1 g.
EXAMPLE 7
Candy Foods Containing Ribose and Caffeine
[0067] Formula I: ribose 100 g, caffeine 200 mg or guarana extract 2 g (containing 10% caffeine), white sugar 200 g, glucose syrup 300 g, vitamin C 3 g, citric acid 30 g, sodium citrate 3 g, apple essence 0.3 g, wolfberry extract 1 g and starch syrup 363 g.
[0068] Formula II: ribose 100 g, caffeine 200 mg or guarana extract 2 g (containing 10% caffeine), starch 25 g, starch syrup 400 g, white sugar 450 g, strawberry juice concentrate 5 g, citric acid 20 g and essences 0.2 g.
[0069] Formula III: ribose 80 g, caffeine 200 mg or guarana extract 2 g (containing 10% caffeine), xylitol 180 g, maltitol 70 g, sorbitol 30 g, mannitol 10 g, gum arabic 20 g, glucose syrup 300 g, gum base 350 g, inulin 50 g, chrysanthemum extract 1 g, pear juice concentrate 4 g, stevia 0.8 g, carnauba wax 2 g and soy lecithin 2 g.
[0070] Formula IV: ribose 6 g, white sugar 10 g, cocoa butter 34 g, cocoa powder 16 g and milk 10 g. The cocoa butter and cocoa powder are placed over a low fire and melted, added with white sugar and milk and heated until the mixture is uniform and sticky. Then ribose is added, melted, mixed evenly, and the resultant mixture is poured into a container model to obtain ribose-containing chocolate.
EXAMPLE 8
Anti-Fatigue Effect of Ribose Plus Coffee
1. Test Method
[0071] Uchida-Kraepelin psychological testing method is used to collect data. 18 healthy subjects (male 8 and female 10), aged 24-48 years old, without heart disease, diabetes and other chronic diseases, are randomly enrolled in the test. The subjects finish their lunch at 12:00, and take the coffee and ribose plus coffee respectively at 13:30, and operation test is performed at 16:00. The operation test requires the subjects to perform a continuous addition calculation of one-digit number under a certain time pressure for 15 minutes. The working status and the fatigue degree of the subjects a period of time after administration of ribose plus coffee and coffee, respectively, are judged by comparing the work amounts and the ratios of the maximum work amount to the minimum work amount. The data are processed according to statistical comparison test (SPSS) to determine the anti-fatigue effects of different beverages.
2. Experimental Materials
[0072] Black coffee (3.6 g, caffeine content 50 mg/bag), ribose plus coffee (Example 3) and 1-9 random number table (10816 compiled by referring to Kraepelin psychological test table).
3. Processing of Results
[0073] The continuous addition calculation test of one-digit number under certain time pressure is performed for 15 minutes for the subjects drinking black coffee and ribose plus coffee, and the resulted data are compared in pairs and analyzed (Tables 2-4).
TABLE-US-00002 TABLE 2 Basic descriptive statistics of 15 minutes continuous calculation test for the subjects drinking black coffee and ribose plus coffee standard mean mean quantity deviations standard error ribose plus 81.6124 11 5.55719 1.67556 coffee black 77.0273 11 6.81265 2.05409 coffee
TABLE-US-00003 TABLE 3 Correlation coefficient and test of 15 minutes continuous calculation for the subjects drinking black coffee and ribose plus coffee quantity Correlation significance ribose plus coffee & 11 0.429 0.188 black coffee 3.8 g
TABLE-US-00004 TABLE 4 test results of paired samples performing 15 minutes continuous calculation for the subjects drinking black coffee and ribose plus coffee Paired samples test 95% confidence signifi- interval Degree cance standard standard Low high T of (two- mean deviation error value value value freedom tailed) ribose plus 4.58509 6.69330 2.01811 .08847 9.08171 2.272 10 .046 pairs coffee- black coffee
[0074] It can be seen from Table 3 that there are significant differences between the data of 15 minutes continuous addition calculation test of one-digit number under a certain time pressure for the subjects drinking ribose plus coffee and black coffee (i.e. P<0.05). The calculated amount of 15 lines continuous operations is taken as the ratio of the maximum calculated amount to the minimum calculated amount, thereby to determine the degree of fatigue. The higher the ratio is, the better the anti-fatigue effect is. It can be seen that anti-fatigue effect of drinking ribose plus coffee on the body is more significant compared to that of drinking black coffee.
[0075] Although the foregoing has been described the present invention in detail with the general description and specific embodiments, but some modifications or improvements can be made based on the present invention, which is obvious to a person skilled in the art. Therefore, these modifications or improvements without departing from the spirit of the invention fall into the scope of the invention as claimed.
INDUSTRIAL APPLICABILITY
[0076] The present invention provides a composition containing ribose and caffeine with long-lasting anti-fatigue effect, which can improve the body's energy and resist short-term and long-term fatigue in the body. The combination of caffeine and ribose can quickly refresh mind and excite spirit, while it can also supplement the energy required by the body and make the body full of physical strength and such state can be sustained. The composition is effective in improving the more tired condition and discomfort after a short time excitement in the body, which is caused by the prior product containing caffeine as main anti-fatigue ingredient, thus making the body maintain their physical strength better.