Application of alpha ketoglutaric acid ferric salt in preparation of health product for improving exercise function and / or improving exercise fatigue

CN119488514APending Publication Date: 2025-02-21SICHUAN UNIV
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Patent Information

Application Number
CN202411863074.8
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-12-17
Publication Date
2025-02-21

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Abstract

The invention discloses an application of alpha ketoglutaric acid ferric salt in preparation of a health product for improving exercise function and / or improving exercise fatigue. Animal tests show that the alpha ketoglutaric acid ferric salt can remarkably improve exercise tolerance and gripping power of mice, can reduce the lactic acid level of serum of the mice, can also improve some enzyme activities in the metabolic process and enhance the metabolic effect of the body, and has the effect remarkably superior to that of pure use of alpha ketoglutaric acid sodium salt. The alpha ketoglutarate ferric salt is applied to enhancing muscle strength, improving the metabolic capacity of the body and reducing factors adverse to the body in the metabolic process, so that the alpha ketoglutarate ferric salt has wide prospects in medicines or health care products for relieving body fatigue and improving exercise ability.
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Description

Technical Field

[0001] The present invention specifically relates to the use of alpha-ketoglutarate iron salt in preparing a health product for improving motor function and / or improving sports fatigue. Background Art

[0002] Fatigue is a normal physiological phenomenon that occurs when mental or physical strength reaches a certain stage. The main manifestation of fatigue is the decrease of body energy and muscle strength during exercise. Anti-fatigue is to delay the occurrence of fatigue and accelerate the elimination of fatigue. Improving endurance and delaying fatigue are important topics in the fields of biological science and nutritional science. With the improvement of living standards and the aggravation of aging, more and more people are beginning to pay attention to physical health and fatigue index.

[0003] At present, most solutions to fight fatigue are to provide energy substrates that are easy to metabolize, such as glucose, fructose, medium- and short-chain fatty acids, and amino acids. There are also solutions that, on the basis of providing energy substrates, further supplement vitamins or trace elements to increase the enzyme activity and oxidative phosphorylation rate in each link of oxidative metabolism and increase the level of ATP generation. However, these solutions can only alleviate fatigue symptoms to a certain extent, and have not fundamentally solved the problem of insufficient intermediates of tricarboxylic acid cycle metabolism that causes fatigue.

[0004] Patent CN106963749A discloses that α-ketoglutaric acid and its salts have the effects of anti-fatigue and improving motor function. However, experiments have found that different α-ketoglutaric acid salts have different effects in anti-fatigue and improving motor function, and not all α-ketoglutaric acid salts have obvious anti-fatigue and motor function improving effects. Therefore, it is necessary to find a specific salt compound from α-ketoglutaric acid salts that can significantly improve motor function and anti-fatigue, so that α-ketoglutaric acid salts can be actually used in health products that improve motor function and improve sports fatigue, so that a wide range of audiences can benefit from it. Summary of the invention

[0005] In order to solve the above problems, the purpose of the present invention is to provide the use of α-ketoglutarate iron salt in the preparation of drugs for improving motor function and / or improving sports fatigue.

[0006] The present invention also provides the use of alpha-ketoglutarate iron salt in preparing a health product for relieving physical fatigue.

[0007] Furthermore, the α-ketoglutarate iron salt has the effect of increasing muscle strength.

[0008] Furthermore, the α-ketoglutarate iron salt has the effect of increasing muscle exercise endurance.

[0009] Furthermore, the α-ketoglutarate iron salt has the effect of delaying the occurrence of fatigue.

[0010] Furthermore, the α-ketoglutarate iron salt has the effect of enhancing body metabolism.

[0011] Furthermore, the α-ketoglutarate iron salt has the effect of inhibiting the activities of lactate dehydrogenase and creatine kinase.

[0012] Furthermore, the medicine is a preparation prepared with α-ketoglutarate iron salt as the active ingredient and pharmaceutically acceptable excipients.

[0013] Furthermore, the medicine is a preparation prepared with α-ketoglutarate iron salt as the active ingredient and auxiliary materials acceptable to health care products.

[0014] Furthermore, the preparation is an oral preparation; the oral preparation includes a solution, a powder, a granule, a tablet, a capsule, a pill or a paste.

[0015] The α-ketoglutarate iron salt of the present invention is used in the preparation of health products for improving motor function and / or improving sports fatigue. The present invention proves through animal experiments that the α-ketoglutarate iron salt can significantly improve the sports endurance and gripping force of mice, and can reduce the serum lactic acid level of mice, and can also regulate some enzyme activities in the metabolic process, enhance the metabolic function of the body, and the effect is significantly better than the use of α-ketoglutarate sodium salt alone. The α-ketoglutarate iron salt is used to enhance muscle strength while improving the metabolic capacity of the body, reducing some unfavorable factors to the body in the metabolic process, so as to relieve body fatigue and improve sports ability. The medicine or health care product has a broad prospect.

[0016] Obviously, according to the above contents of the present invention, in accordance with common technical knowledge and customary means in the art, without departing from the above basic technical ideas of the present invention, other various forms of modification, replacement or change may be made.

[0017] The above contents of the present invention are further described in detail below through specific implementation methods in the form of embodiments. However, this should not be understood as the scope of the above subject matter of the present invention being limited to the following examples. All technologies realized based on the above contents of the present invention belong to the scope of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 The effect of α-ketoglutarate iron salt on muscle strength of normal C57BL / 6J mice.

[0019] Figure 2 The effect of α-ketoglutarate iron salt on the motor ability of normal C57BL / 6J mice.

[0020] Figure 3 The effect of α-ketoglutarate iron salt on blood biochemical parameters of C57BL / 6J mice.

[0021] Figure 4 The effect of α-ketoglutarate iron salt on the activity of exercise metabolic enzyme - LDH in C57BL / 6J mice.

[0022] Figure 5 The effect of α-ketoglutarate iron salt on the activity of exercise metabolic enzyme -CK in C57BL / 6J mice. DETAILED DESCRIPTION

[0023] Example 1 Study on the Effect of α-Ketoglutarate on Motor Performance and Muscle Strength in Mice

[0024] 1. Experimental animals and groups

[0025] Mice were used as the research subjects. 40 5-week-old C57BL / 6J mice were selected and divided into 4 groups on average, as follows:

[0026] Control group: drinking sterile water;

[0027] Treatment group 1: 1% α-ketoglutarate sodium salt solution (αKG-Na) was added to drinking water;

[0028] Treatment group 2: 1% α-ketoglutarate iron solution (αKG-Fe) was added to drinking water.

[0029] The pH of drinking water was adjusted to 7.0 in each group, and the mice were allowed to eat and drink freely. The mice were placed under 12-mice cycle lighting, and the ambient humidity was 70% ± 10%, and the temperature was kept constant at 23°C ± 1°C. The mice were fed with or without 1% α-ketoglutarate iron or sodium salt in drinking water for 8 weeks for the detection of muscle strength and exercise time.

[0030] 2. Muscle strength and exercise ability test

[0031] 2.1 Determination of the effect of α-ketoglutarate iron salt on muscle strength of normal C57BL / 6J mice

[0032] (1) Detection method

[0033] The mice were raised to 8 weeks old, and 10 mice in each group were placed on the grip strength instrument for 3 sets of 10 consecutive tensile tests. The maximum tensile value of each test was recorded, and the average value of the maximum value of each test was taken for statistical analysis.

[0034] (2) Test results

[0035] The results are as follows Figure 1 As shown, from Figure 1 It can be seen that feeding mice with 1% α-ketoglutarate iron salt in drinking water for 8 weeks can significantly increase the muscle grip strength of mice (P<0.05), which is more obvious than the group with only α-ketoglutarate sodium salt. This shows that α-ketoglutarate iron salt can more significantly increase the muscle strength of mice.

[0036] 2.2. Determination of the effect of α-ketoglutarate iron salt on the motor ability of normal C57BL / 6J mice

[0037] (1) Detection method

[0038] Mice were raised to 8 weeks old, and 10 mice were taken from each group for exercise test. The inclination angle of the small animal treadmill was adjusted to 10°, and 10 mice were taken from each group to exercise at a speed of 10m / min on the small animal treadmill (Chengdu Taimeng Software Co., Ltd., FT-201). After the exercise, the mice rested for 10min. After the rest, the mice were given a speed of 10m / min, and then the speed of the mice increased by 1m / min every 3min until the maximum speed increased to 20m / min, until the mice were exhausted, and the total exercise time of the mice was recorded. Exhaustion standard: the limbs are unable to support the body, the head is drooping, and continuous electrical stimulation within 30s cannot make it run 10 times, which means the mouse is exhausted.

[0039] (2) Test results

[0040] The results are as follows Figure 2 As shown, from Figure 2 It can be seen that compared with the control group, feeding mice with 1% α-ketoglutarate iron salt in drinking water for 8 weeks can significantly increase the mice's exercise time (P<0.05), and is significantly better than the group with only α-ketoglutarate sodium salt, indicating that α-ketoglutarate iron salt can increase the exercise endurance of mouse muscles.

[0041] From the above results, it can be seen that compared with simple administration of water and water containing α-ketoglutarate sodium salt, adding 1% α-ketoglutarate iron salt to drinking water can significantly increase the muscle grip strength and exercise endurance of mice, indicating that α-ketoglutarate iron salt can significantly increase the muscle strength and exercise endurance of mice.

[0042] Example 2 Study on the Effect of α-ketoglutarate on Blood Biochemical Indexes in Mice

[0043] 1. Experimental animals and groups

[0044] Mice were used as the research subjects. 40 5-week-old C57BL / 6J mice were selected and divided into 4 groups on average, as follows:

[0045] Control group: drinking sterile water;

[0046] Treatment group 1: 1% α-ketoglutarate sodium salt solution (αKG-Na) was added to drinking water;

[0047] Treatment group 2: 1% α-ketoglutarate iron solution (αKG-Fe) was added to drinking water.

[0048] The pH of drinking water was adjusted to 7.0 for each group, and they were allowed to eat and drink freely. The lighting cycle was 12h / 12h, the humidity was 70±10%, and the temperature was constant at 23±1°C. Blood was collected from mice through the ocular vein after 8 weeks of feeding, with or without the addition of 1% α-ketoglutarate iron or sodium salt to drinking water.

[0049] 2. Determination of the effects of α-ketoglutarate iron salt on blood biochemical parameters of C57BL / 6J mice

[0050] (1) Detection method

[0051] C57BL / 6J mice were given 1% α-ketoglutarate iron salt in drinking water. After 8 weeks of feeding, blood was collected from the mice through the ocular vein, and serum was separated and the serum lactate level was detected using a lactate detection kit (Nanjing Jiancheng Biotechnology Co., Ltd.).

[0052] (3) Test results

[0053] The results are as follows Figure 3 As shown, Figure 3 The results showed that compared with water alone and water with α-ketoglutarate sodium salt, adding 1% α-ketoglutarate iron salt to drinking water can significantly reduce the serum lactate content of C57BL / 6J mice. Lactic acid is one of the important factors of sports fatigue. During strenuous exercise, the large accumulation of lactic acid will cause the muscle pH value to decrease, thereby causing fatigue. Therefore, lowering the blood lactate content can effectively delay the onset of fatigue. This shows that α-ketoglutarate iron salt has a more significant ability to delay the occurrence of fatigue in mice.

[0054] Example 3 Study on the Effect of α-Ketoglutarate on the Activity of Exercise Metabolic Enzymes in Skeletal Muscle of Mice

[0055] 1. Experimental animals and groups

[0056] Mice were used as the research subjects. 40 5-week-old C57BL / 6J mice were selected and divided into 4 groups on average, as follows:

[0057] Control group: drinking sterile water;

[0058] Treatment group 1: 1% α-ketoglutarate sodium salt solution (αKG-Na) was added to drinking water;

[0059] Treatment group 2: 1% α-ketoglutarate iron solution (αKG-Fe) was added to drinking water.

[0060] The pH of drinking water was adjusted to 7.0 in the above groups. The animals were allowed to eat and drink freely, and the lighting cycle was 12h / 12h. The humidity was 70%±10%, and the temperature was kept constant at 23℃±1℃. The animals were fed with or without 1% α-ketoglutarate iron or sodium salt in drinking water for 8 weeks.

[0061] 2. Determination of the effect of α-ketoglutarate iron salt on skeletal muscle motor metabolic enzymes in C57BL / 6J mice

[0062] (1) Detection method

[0063] C57BL / 6J mice were given 1% α-ketoglutarate iron salt in drinking water. After 8 weeks of feeding, the mice were allowed to run slowly at a speed of 20 m / min for 30 min. After the experiment, the gastrocnemius of the mice was collected and stored in a -80°C refrigerator for later use. The muscle tissue fluid was obtained by homogenization and separation using a high-speed homogenizer with 0.9% NaCl solution for total protein concentration (ThermoBCA kit) and exercise metabolism enzyme activity kit detection, including lactate dehydrogenase and creatine kinase enzyme activity detection kits (Nanjing Jiancheng Biotechnology Co., Ltd.).

[0064] (2) Test results

[0065] The results are as follows Figures 4-5 As shown in the figure, it can be seen that adding 1% α-ketoglutarate iron salt to drinking water can significantly inhibit the activity of lactate dehydrogenase (LDH) and inhibit the content of creatine kinase (CK). LDH is an enzyme that catalyzes the conversion between lactate and pyruvate. In higher-intensity exercise, LDH helps to reduce pyruvate to lactate in this process in order to maintain the supply of ATP. As the intensity of exercise decreases or in the recovery phase after exercise, LDH oxidizes lactate to pyruvate and enters the mitochondria for further aerobic metabolism, thereby avoiding excessive accumulation of lactate. The experiment measured the instantaneous lactate dehydrogenase concentration of mice after exhaustion caused by high-intensity exercise. The activity of lactate dehydrogenase was inhibited, indicating that lactate accumulation was reduced, and the muscle fatigue and soreness caused by lactate accumulation could be relieved. CK is an important biomarker of muscle damage. A decrease in its level usually means a reduction in the degree of muscle damage. A decrease in serum creatine kinase levels indicates that muscle soreness symptoms are relieved. Compared with normal drinking water, the simple administration of α-ketoglutarate sodium salt could not significantly reduce the activity of LDH in serum (p>0.05), and the reduction of serum CK content was only statistically significant (p<0.05), while the simple administration of α-ketoglutarate iron salt could significantly reduce the activity of LDH (p<0.05) and extremely significantly reduce the CK content (p<0.001). This indicates that α-ketoglutarate iron salt can enhance the metabolism of α-ketoglutarate after exercise, enhance exercise capacity, and delay the fatigue degree of mice, and is significantly better than the simple administration of α-ketoglutarate sodium salt group.

[0066] In summary, the animal experiments of the present invention show that α-ketoglutarate iron salt can significantly improve the exercise endurance and grip strength of mice, reduce the serum lactate level of mice, regulate the activity of metabolism-related enzymes, and enhance the body's metabolic function, and the effect is significantly better than the use of α-ketoglutarate sodium salt alone. The application of α-ketoglutarate iron salt to enhance muscle strength while improving the body's metabolic capacity, reducing some unfavorable factors to the body during metabolism, and relieving body fatigue and improving exercise capacity has broad prospects in medicines or health products.

Claims

1. Use of α-ketoglutarate iron salt in the preparation of medicines for improving motor function and / or improving sports fatigue.

2. Use of α-ketoglutarate iron salt in the preparation of health products for relieving physical fatigue.

3. The use according to claim 1 or 2, characterized in that: The alpha-ketoglutarate iron salt has the effect of increasing muscle strength.

4. The use according to claim 1 or 2, characterized in that: The alpha-ketoglutarate iron salt has the effect of increasing muscle exercise endurance.

5. The use according to claim 1 or 2, characterized in that: The alpha-ketoglutarate iron salt has the effect of delaying the occurrence of fatigue.

6. The use according to claim 1 or 2, characterized in that: The alpha-ketoglutarate iron salt has the effect of enhancing body metabolism.

7. The use according to claim 6, characterized in that: The α-ketoglutarate iron salt has the function of inhibiting the activities of lactate dehydrogenase and creatine kinase.

8. The use according to claim 1, characterized in that: The medicine is a preparation prepared by taking α-ketoglutarate iron salt as the active ingredient and adding pharmaceutically acceptable auxiliary materials.

9. The use according to claim 2, characterized in that: The health care product is a preparation prepared by taking alpha-ketoglutarate iron salt as an active ingredient and adding auxiliary materials acceptable to health care products.

10. The use according to claim 8 or 9, characterized in that: The preparation is an oral preparation; the oral preparation includes solution, powder, granule, tablet, capsule, pill or paste.