Composition for preventing or / and treating plateau hypoxic fatigue and preparation method and application thereof

Abstract

The invention provides a composition for preventing or / and treating plateau hypoxic fatigue. The composition is prepared from the following raw materials in parts by weight: 24-48 parts of an emblic leafflower fruit extract, 24-40 parts of a ginseng extract, 24-48 parts of a sea-buckthorn extract and 25 parts of coffee powder. The invention also provides a preparation method and application of the composition. The composition disclosed by the invention can quickly exert an anti-fatigue effect, experiments prove that all the raw materials are matched for use, a synergistic interaction effect can be exerted, and the composition can be quickly dissolved in an oral cavity, is excellent in taste and can be taken without water, and the invention provides a medicinal and edible health product for preventing or treating plateau hypoxia fatigue.

Description

TECHNICAL FIELD

[0001] The present application relates to a composition for preventing or / and treating hypoxic fatigue at high altitude. BACKGROUND

[0002] With the increasing demand for high-altitude tourism, sports competition and other needs, the number of activities in high-altitude areas is increasing, but the low oxygen and high altitude environment unique to high-altitude areas can cause hypoxic fatigue and other symptoms in the human body. Hypoxic fatigue at high altitude is one of the most common subjective discomforts during acute and chronic high-altitude exposure, and its mechanism involves a complex network from cellular oxygen sensing to peripheral-central integrated regulation.

[0003] The altitude in high-altitude areas is generally around 1000-5000 meters. People from plain areas will experience headache, dizziness, tinnitus, insomnia and other high-altitude acclimatization disorders during the initial stage of rapid entry into high-altitude areas, and after long-term life and work in high-altitude areas, there are still problems such as hypoxic fatigue, sleep disorders, and mental fatigue. Therefore, it is necessary to research and develop a health product with medicinal and edible properties to prevent or treat hypoxic fatigue at high altitude.

[0004] Research has found that high-altitude hypoxia symptoms can be prevented or improved by consuming high-altitude anti-hypoxia plants. Rhodiola is one of the plants recognized worldwide, but long-term use can have certain side effects on the body. Medicinal and edible plants have fewer side effects and are easy to eat, and have become a hot spot in recent years for anti-hypoxic fatigue research. High-altitude characteristic biological resources such as highland barley, wolfberry, sea buckthorn, and Nitraria tangutorum Bobr have anti-hypoxic and anti-fatigue effects when used alone, but there are few reports on their combined use in acute hypoxic environments (Chen, et al., Anti-fatigue effect of highland characteristic nutritional powder on BALB / C mice in simulated high-altitude environment, Grain and Oil, 2024, Vol. 37, No. 10.

[0005] Zhang, et al., Experimental study on the anti-fatigue effect of Phyllanthus emblica on mice in a simulated high-altitude environment, Journal of Pharmacy of the Chinese People's Liberation Army, June 20, 2011, Vol. 27, No. 3, observed the effect of Phyllanthus emblica on improving the anti-fatigue ability of mice in a simulated high-altitude environment. Ginseng also has hypoxia tolerance and anti-fatigue effects (Li, et al., Research progress of Chinese medicine in preventing and treating high-altitude hypoxia, World Science and Technology - Modernization of Chinese Medicine, Chinese Medicine Research, Vol. 23, No. 12) There is currently no related report on the combination of Phyllanthus emblica extract, ginseng extract, sea buckthorn extract, and coffee powder for high-altitude hypoxic fatigue. SUMMARY

[0006] The present application provides a composition for preventing or / and treating hypoxic fatigue at high altitude, as well as a preparation method and use thereof.

[0007] The present application also provides a composition for preventing or / and treating high altitude hypoxic fatigue, which is prepared from the following raw materials in the following proportions by weight: Phyllanthus emblica extract 24-48 parts, ginseng extract 24-40 parts, sea buckthorn extract 24-48 parts, coffee powder 25 parts.

[0008] Preferably, it is prepared from the following raw materials in the following proportions by weight: Phyllanthus emblica extract 30 parts, ginseng extract 25 parts, sea buckthorn extract 15 parts, coffee powder 15 parts.

[0009] It is prepared from the following raw materials in the following proportions by weight: Phyllanthus emblica extract 48 parts, ginseng extract 40 parts, sea buckthorn extract 24 parts, coffee powder 25 parts.

[0010] The preparation method of the Phyllanthus emblica extract is as follows: fresh Phyllanthus emblica fruit is refluxed, concentrated, and spray-dried to prepare a powdered raw material; The preparation method of the sea buckthorn extract is as follows: fresh sea buckthorn fruit is decocted, concentrated, and dried to prepare a powdered raw material; The preparation method of the ginseng extract is as follows: ginseng stems and leaves are pulverized, refluxed, concentrated, and dried to prepare a powdered raw material; The preparation method of the coffee powder is as follows: coffee beans are dried, pulverized, and sieved to prepare a powdered raw material.

[0011] It is prepared from the active ingredients in the proportions by weight, with the addition of pharmaceutically or food acceptable excipients or auxiliary ingredients, into the oral preparations commonly used in pharmacy or food.

[0012] The present application also provides a preparation method of the composition for preventing or / and treating high altitude hypoxic fatigue, which comprises the following steps: a. taking raw materials in the proportions by weight; b. after mixing, adding pharmaceutically or food acceptable excipients or auxiliary ingredients to prepare a preparation commonly used in pharmacy or food.

[0013] After mixing in step b, the ultrafine grinder is used for low-temperature grinding and pulverization.

[0014] The present application provides the use of the composition in the preparation of a medicine for preventing or / and treating high altitude hypoxic fatigue.

[0015] The present application provides the use of the composition in the preparation of a health product for helping to relieve physical fatigue.

[0016] The present application provides the use of the composition in the preparation of a health product with hypoxia tolerance.

[0017] The composition can quickly exert an anti-fatigue effect, experiments prove that the raw materials are used in combination to exert a synergistic effect, and are quickly dissolved in the oral cavity, have excellent taste, and realize waterless delivery. BRIEF DESCRIPTION OF DRAWINGS

[0018] Figure 1 The exhaustive swimming time of mice in each group (compared with the group formula group, *p<0.05, **p<0.01, ***p<0.001; compared with the normoxic group, #p<0.05, ##p<0.01, ###p<0.001); Figure 2 The serum LDH activity and BUN content of mice in each group after exhaustive swimming (compared with the group formula group, *p<0.05, **p<0.01, ***p<0.001; compared with the normoxic group, #p<0.05, ##p<0.01, ###p<0.001); Figure 3 The serum MDA content and T-AOC activity of mice in each group after exhaustive swimming (compared with the group formula group, *p<0.05, **p<0.01, ***p<0.001; compared with the normoxic group, #p<0.05, ##p<0.01, ###p<0.001); Figure 4 The serum TG and liver glycogen content of mice in each group after exhaustive swimming (compared with the group formula group, *p<0.05, **p<0.01, ***p<0.001; compared with the normoxic group, #p<0.05, ##p<0.01, ###p<0.001); Figure 5 The exhaustive swimming time of mice in each group (compared with the hypoxia group, *p<0.05, **p<0.01, ***p<0.001; compared with the normoxic group, #p<0.05, ##p<0.01, ###p<0.001); Figure 6 The serum LDH activity and BUN content of mice in each group after exhaustive swimming (compared with the hypoxia group, *p<0.05, **p<0.01, ***p<0.001; compared with the normoxic group, #p<0.05, ##p<0.01, ###p<0.001); Figure 7 The serum MDA content and T-AOC activity of mice in each group after exhaustive swimming (compared with the hypoxia group, *p<0.05, **p<0.01, ***p<0.001, ns no statistical significance; compared with the normoxic group, #p<0.05, ##p<0.01, ###p<0.001); Figure 8The serum TG and liver glycogen contents of each group of mice after exhaustive swimming were measured (compared with the hypoxia group, *p<0.05, **p<0.01, ***p<0.001; compared with the normoxia group, #p<0.05, ##p<0.01, ###p<0.001). DETAILED DESCRIPTION

[0019] Example 1 Preparation of the composition of the present application 1. Emblica extract: Emblica fresh fruit is prepared into powder raw material by reflux, concentration, and spray drying 2. Sea buckthorn extract: Sea buckthorn fresh fruit is prepared into powder raw material by decocting, concentrating, and drying 3. Ginseng extract: Ginseng stem and leaf is prepared into powder raw material by crushing, refluxing, concentrating, and drying 4. Coffee powder: Coffee beans are prepared into powder raw material by drying, crushing, and sieving.

[0020] Among them, the Emblica extract, the ginseng extract, and the sea buckthorn extract can also be commercially available, and the manufacturer is Fufeng Snoot Biotechnology Co., Ltd.; the instant coffee powder manufacturer is Ximu Foodstuff (Shanghai) Co., Ltd.

[0021] The preparation process is as follows: Preparation process: 96 g of Emblica extract, 48 g of ginseng extract, 80 g of sea buckthorn extract, 50 g of coffee powder, 52 g of sucrose, and 200 g of xylitol are taken into a SYFM-8 II type vibration type drug ultrafine grinder for low-temperature grinding and crushing for 8 minutes to obtain an ultrafine powder mixture raw material for standby, and then 270 g of erythritol and 16 g of silicon dioxide are mixed with the above mixture raw material for low-temperature crushing for 2 minutes, and the mixture is precisely packaged and sterilized to obtain the finished product.

[0022] The beneficial effects of the present application are demonstrated by the following efficacy tests.

[0023] Test Example 1 Anti-high-altitude hypoxia fatigue test of the composition of the present application I. Functional evaluation: C57 mice are raised in an environment with a temperature of 23-27℃ and a relative humidity of 50%-60%, with 12 h light and dark alternation, and free feeding and drinking.

[0024] Normoxia control group: in a plain oxygen concentration environment, physiological saline is administered once a day for 7 days; Hypoxia model group: simulated 5000 m altitude oxygen concentration, physiological saline is administered once a day for 7 days; Positive control group: simulated 5000 m altitude oxygen concentration, Rhodiola capsule as positive drug (0.5 g / kg), for 7 days The formulation included high, medium, and low dose groups: simulating oxygen concentration at an altitude of 5000 m, with high dose (8 g / Kg·d), medium dose (4 g / Kg·d), and low dose (1.6 g / Kg·d). The dosage was 0.1 mL / 10 g for 7 consecutive days, all based on mouse dosage.

[0025] Formula group: simulated oxygen concentration at an altitude of 5000 m, the dosage was 4.9 g / Kg·d, for 7 consecutive days, the dosage was 0.1 mL / 10 g, all based on mouse dosage.

[0026] Phyllanthus emblica extract group: Simulating oxygen concentration at an altitude of 5000 m, the dosage was 4.9 g / Kg·d for 7 consecutive days, and the dosage was 0.1 mL / 10 g, all based on mouse dosage.

[0027] Ginseng extract group: Simulating oxygen concentration at an altitude of 5000 m, the dosage was 4.9 g / Kg·d for 7 consecutive days, and the dosage was 0.1 mL / 10 g, all based on mouse dosage.

[0028] Sea buckthorn extract group: Simulating oxygen concentration at an altitude of 5000 m, the dosage was 4.9 g / Kg·d for 7 consecutive days, and the dosage was 0.1 mL / 10 g, all based on mouse dosage.

[0029] Instant coffee powder group: Simulating oxygen concentration at an altitude of 5000 m, the dosage was 4.9 g / Kg·d for 7 consecutive days, with a dosage of 0.1 mL / 10 g, all based on mouse dosage.

[0030] Formula 1: Phyllanthus emblica extract: Hippophae rhamnoides extract: Ginseng extract: Coffee powder: Sucrose (48:24:40:25:26), dosage was 1.6 g / kg·d for 7 consecutive days, dosage was 0.1 mL / 10 g, all based on mouse dosage.

[0031] Formula 2: Phyllanthus emblica extract: Hippophae rhamnoides extract: Ginseng extract: Coffee powder: Sucrose (24:48:40:25:26), the dosage was 1.6 g / kg·d for 7 consecutive days, the dosage was 0.1 mL / 10 g, all based on mouse dosage.

[0032] Formula 3: Phyllanthus emblica extract: Hippophae rhamnoides extract: Ginseng extract: Coffee powder: Sucrose (40:24:24:25:26), dosage was 1.6 g / kg·d for 7 consecutive days, dosage was 0.1 mL / 10 g, all based on mouse dosage.

[0033] Preventive medication is administered one week before entering the hypobaric oxygen chamber.

[0034] 1. Time to exhaustion while swimming Compared with the normoxic control group, the time to exhaustion in the hypoxic model group of mice was significantly shorter, showing a statistically significant difference. p< 0.05), indicating that hypoxia reduces the exercise capacity of mice. Compared with the hypoxic model group, the time to exhaustion in re-swimming was significantly prolonged in all drug-treated groups ( p< 0.001). Meanwhile, the swimming exhaustion time of the mice in the formulation group was significantly increased compared to the positive control group. This indicates that the formulation can effectively enhance the effect of each individual herb in improving hypoxic fatigue in mice and prolonging their swimming exhaustion time. Figure 1 Meanwhile, among different formulations, ratio 1 had a stronger effect on increasing the time to exhaustion in mice (Table 1).

[0035] Table 1. Improvement in motor behavior and changes in serum biochemical parameters in mice under different formulation ratios (X±SD, n=6, compared with formulation 1, *) p <0.05,** p <0.01, *** p <0.001)

[0036] 2. Serum biochemical indicators 2.1 Lactate dehydrogenase (LDH) and serum urea nitrogen (BUN) Increased lactate accumulation tends to lead to increased LDH activity. BUN is the final product of protein catabolism, and changes in serum BUN levels indicate kidney function. Therefore, changes in serum LDH activity and serum BUN levels can serve as important indicators for assessing exercise-induced fatigue. Figure 2 It can be seen that compared with the normoxic control group, the serum LDH activity and BUN content were both increased in the hypoxia model group. p< 0.001); Meanwhile, compared with the hypoxia model group, the LDH activity and BUN content in each treatment group were significantly reduced ( p < (0.001); This indicates that after administration, the increase in serum LDH activity and BUN content in mice caused by hypoxia can be inhibited. However, the decrease in LDH activity and BUN content was greater in the group treated with this formulation compared to other treatment groups. At the same time, the inhibitory effect of formulation 1 on LDH activity and BUN content was also better than that of other formulations (Table 1).

[0037] 2.2 MDA content and total antioxidant capacity (T-AOC) activity MDA is a metabolite of lipid peroxidation and can indirectly reflect the degree of cell damage caused by oxygen free radicals. Figure 3 It can be seen that, compared with the normoxic control group, the serum MDA content in the hypoxic model group mice was significantly increased. p<0.001), T-AOC activity was significantly reduced ( p< The result was 0.05, indicating that hypoxic environments cause an increase in serum MDA levels and a decrease in T-AOC activity. Compared with the hypoxic model group, all treatment groups showed a decrease in MDA levels and an increase in T-AOC activity. In contrast, the formulation group significantly reduced the content of lipid metabolite MDA and significantly increased T-AOC activity. p< 0.001). This indicates that the formulation can enhance the ability of each individual herb to inhibit the increase in serum MDA content and decrease in T-AOC activity in mice caused by hypoxia. Formulation 1 also showed a stronger ability to reduce MDA content and increase T-AOC activity than the other two groups (Table 1).

[0038] 2.3 Triglycerides (TG) and Glycogen (Glu) pass Figure 4 It can be seen that, compared with the normoxic model group, the serum TG level in the hypoxic model group mice decreased slightly, but this was not statistically significant. Other drug administration groups also had almost no effect on TG levels, and there was almost no difference in TG changes among the three different drug ratios (Table 1). However, compared with the normoxic model group, the glycogen content in the liver of the hypoxic model group mice decreased extremely significantly. p< The result was 0.001, indicating that mice consume liver glycogen as a raw material for energy metabolism under hypoxic conditions; compared with the hypoxic model group, each treatment group significantly increased the liver glycogen content in mice. p< (0.001), the formulation group showed an even greater increase. This indicates that the formulation can significantly increase the level of energy substances in the body, and the ratio of 1 to 1 shows an even greater increase in energy substances.

[0039] In conclusion, the combination of individual herbs can enhance their ability to resist hypoxic fatigue and exert a synergistic effect. The ratio 1: Phyllanthus emblica: Hippophae rhamnoides: Ginseng: Coffee powder: Sucrose (48:24:40:25:26) is even more effective. The ratio 1 will be selected for subsequent experiments.

[0040] Experimental Example 2: Pharmacodynamic Study of the Composition of the Invention 1. Time to exhaustion while swimming like Figure 5 As shown, compared with the normoxic control group, the time to exhaustion during swimming was significantly shorter in the hypoxic model group, with a statistically significant difference. p< 0.05), indicating that hypoxia reduces the exercise capacity of mice. Compared with the hypoxia model group, the time to exhaustion in reswimming was significantly prolonged in the low-dose, medium-dose, and high-dose formulations. p<(0.001). Meanwhile, the swimming exhaustion time of mice in the medium-dose and high-dose groups was increased compared to the positive control group. This indicates that the formula can effectively improve hypoxic fatigue in mice and prolong their swimming exhaustion time.

[0041] 2. Serum biochemical indicators 2.1 Lactate dehydrogenase (LDH) and serum urea nitrogen (BUN) Increased lactate accumulation tends to lead to increased LDH activity. BUN is the final product of protein catabolism, and changes in serum BUN levels indicate kidney function. Therefore, changes in serum LDH activity and serum BUN levels can serve as important indicators for assessing exercise-induced fatigue. Figure 6 It can be seen that compared with the normoxic control group, the serum LDH activity and BUN content were both increased in the hypoxia model group. p< 0.001); Meanwhile, compared with the hypoxia model group, the LDH activity and BUN content in the Rhodiola rosea positive group and the low, medium, and high dose formulation groups were significantly reduced ( p< 0.001); This indicates that the formula can inhibit the increase in serum LDH activity and BUN content in mice caused by hypoxia.

[0042] 2.2 MDA content and total antioxidant capacity (T-AOC) activity MDA is a metabolite of lipid peroxidation and can indirectly reflect the degree of cell damage caused by oxygen free radicals. Figure 7 It can be seen that, compared with the normoxic control group, the serum MDA content in the hypoxic model group mice was significantly increased. p< 0.001), T-AOC activity was significantly reduced ( p< The result was 0.05, indicating that hypoxia causes an increase in serum MDA levels and a decrease in T-AOC activity. While the low-dose formulation showed a decrease in MDA levels and an increase in T-AOC activity compared to the hypoxia model group, this was not statistically significant. In contrast, the Rhodiola rosea positive group, the medium-dose formulation, and the high-dose formulation all significantly reduced the levels of the lipid metabolite MDA. p< 0.001); Rhodiola rosea positive group and medium dose group of the formula can significantly improve T-AOC activity ( p< 0.05), the high-dose formulation significantly increased T-AOC activity ( p< 0.001). This indicates that the formula can inhibit the increase in serum MDA content and decrease in T-AOC activity in mice caused by hypoxia.

[0043] 2.3 Triglycerides (TG) and Glycogen (Glu) pass Figure 8It can be seen that, compared with the normoxic model group, the serum TG level in the hypoxic model group mice was slightly decreased, but this was not statistically significant. Meanwhile, the positive control group and the high, medium, and low dose groups of the formulation had almost no effect on TG levels. However, compared with the normoxic model group, the liver glycogen content in the hypoxic model group mice was significantly decreased. p< 0.001), indicating that mice consume liver glycogen as a raw material for energy metabolism under hypoxic conditions; compared with the hypoxic model group, the positive group and the high, medium and low dose groups of the formula can significantly increase the liver glycogen content of mice ( p< 0.001). This indicates that the formula can alleviate physical fatigue by increasing the level of energy substances in the body.

Claims

1. A composition for preventing and / or treating altitude sickness-induced fatigue, characterized in that: It is prepared from the following raw materials in the following weight ratio: 24-48 parts of Phyllanthus emblica extract, 24-40 parts of ginseng extract, 24-48 parts of Hippophae rhamnoides extract, and 25 parts of coffee powder.

2. The composition for preventing and / or treating altitude-induced hypoxia-induced fatigue according to claim 1, characterized in that: It is prepared from the following raw materials in the following weight ratio: 48 parts of amla extract, 40 parts of ginseng extract, 24 parts of sea buckthorn extract, and 25 parts of coffee powder.

3. The composition for preventing and / or treating altitude-induced hypoxia-induced fatigue according to claim 1 or 2, characterized in that: The preparation method of the amla extract is as follows: fresh amla fruit is refluxed, concentrated, and spray-dried to prepare a powdered raw material; The preparation method of the sea buckthorn extract is as follows: fresh sea buckthorn fruit is decocted, concentrated, and dried to prepare powder raw material; The method for preparing the ginseng extract is as follows: ginseng stems and leaves are pulverized, refluxed, concentrated, and dried to prepare powder raw materials; The method for preparing the coffee powder is as follows: coffee beans are dried, crushed, and sieved to prepare a powdered raw material.

4. The composition for preventing and / or treating high-altitude hypoxia fatigue according to any one of claims 1-3, characterized in that: It is prepared from the raw materials in the stated weight ratio as active ingredients, with the addition of pharmaceutically or food-acceptable excipients or auxiliary ingredients to form a commonly used oral preparation in pharmaceuticals or food.

5. A method for preparing the composition for preventing and / or treating high-altitude hypoxia fatigue according to any one of claims 1-4, characterized in that: It includes the following steps: a. Take the raw materials in the specified weight proportions; b. After mixing, add pharmaceutically or food-acceptable excipients or auxiliary ingredients to prepare a pharmaceutically or food-common formulation.

6. The method for preparing the composition for preventing and / or treating altitude-induced hypoxia-induced fatigue according to claim 5, characterized in that: After mixing in step b, the mixture is ground and pulverized at low temperature using an ultrafine pulverizer.

7. Use of the composition according to any one of claims 1-4 in the preparation of a medicament for the prevention and / or treatment of altitude-induced hypoxia-induced fatigue.

8. Use of the composition according to any one of claims 4 in the preparation of a health product that helps relieve physical fatigue.

9. Use of the composition according to any one of claims 4 in the preparation of a health product having hypoxia resistance.

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