Application of levetiracetam in preparation of anti-fatigue medicine

Abstract

The invention belongs to the technical field of medicines, and particularly relates to an application of levetiracetam in preparation of an anti-fatigue medicine, and the levetiracetam is proved to be capable of remarkably prolonging running time and swimming time of a mouse through systematic mouse experiments. Therefore, the levetiracetam has a remarkable effect on enhancing the exercise tolerance of the body. The levetiracetam becomes an effective anti-fatigue medicine for people who need to do physical activities or exercises for a long time, such as athletes, soldiers and workers, and helps the people to improve the athletic performance and the working efficiency. In an in-vitro muscle endurance test, it is clear that levetiracetam significantly improves the fatigue index of mouse muscles. The result shows that levetiracetam can directly act on muscular tissues to improve the fatigue state of the muscular tissues. For people who often do high-intensity physical activities, levetiracetam is helpful for relieving muscle fatigue and injury.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical technology, and particularly relates to the application of levetiracetam in the preparation of anti-fatigue drugs. Background Art

[0002] Levetiracetam, chemically known as (S)-α-ethyl-2-oxo-1-pyrrolidineacetamide, is a broad-spectrum anti-epileptic drug that has been widely used globally. It effectively controls epileptic seizures by regulating the release of neurotransmitters and inhibiting the overexcitation of neurons, and has significant clinical efficacy and good safety. The main pharmacological mechanism of levetiracetam involves binding to the synaptic vesicle protein SV2A, and this binding may affect the process of neurotransmitter release, thereby reducing the overexcitation of neurons and achieving the anti-epileptic effect. In addition, levetiracetam may also enhance its control effect on epilepsy by regulating other neurotransmitter systems, such as the γ-aminobutyric acid (GABA) system.

[0003] In the field of drug research and development, the re-development of known drugs and the exploration of new indications have become an important trend. By deeply studying the pharmacological mechanisms and clinical application effects of known drugs, scientists can discover their potential value in other therapeutic fields, thereby expanding the application scope of drugs. This strategy can not only shorten the new drug R & D cycle, reduce R & D costs, but also provide more and more effective treatment options for patients. In recent years, with the in-depth study of the pharmacological mechanism of levetiracetam, scientists have begun to explore the application possibilities of levetiracetam in non-epileptic fields. Although the specific clinical application research is still in its infancy, some preliminary studies have shown that levetiracetam may play a role in certain neurological diseases or symptoms. These studies provide new ideas and directions for the further development and application of levetiracetam.

[0004] Fatigue is a complex physiological state that involves multiple aspects such as the central nervous system, muscular system, and metabolic system. In modern society, due to the accelerating pace of life and increasing work pressure, fatigue has become an important factor affecting people's quality of life and work efficiency. However, the current treatment methods for fatigue are relatively limited and have many deficiencies. Traditionally, the treatment drugs for fatigue mainly include central excitatory drugs, nutritional supplements, traditional Chinese medicines, and medicinal diets. However, these drugs often have problems such as drug addiction, affecting biological rhythms, and slow onset of action, and it is difficult to meet the needs of the majority of patients.

[0005] In summary, as a broad-spectrum anti-epileptic drug with broad application prospects, the application research of levetiracetam in non-epileptic fields is gradually becoming one of the hotspots in the field of drug research and development. The proposal and implementation of the present invention will open up a new path for the further development and application of levetiracetam as a treatment drug for fatigue. Summary of the Invention

[0006] The object of the present invention is to provide an application of levetiracetam in the preparation of an anti - fatigue drug. Levetiracetam is a drug approved by the FDA for marketing. By adding an indication, this drug can be quickly used for the treatment of fatigue, solving the problems of long time for developing anti - fatigue drugs and few drug researches at present.

[0007] The object of the present invention is achieved through the following technical solutions: The present invention provides an application of levetiracetam in the preparation of an anti - fatigue drug.

[0008] Further, the levetiracetam can enhance the exercise endurance of the body and improve its fatigue state.

[0009] Further, the levetiracetam can prolong the time of muscle continuous contraction leading to fatigue.

[0010] Further, the dosage forms of the drug include tablets, capsules, oral preparations and injections.

[0011] Further, the tablets include coated tablets.

[0012] Further, the oral preparations include oral liquid preparations, oral granules and oral powders.

[0013] Further, the injections include freeze - dried powder injections and emulsion for injection.

[0014] The present invention also provides an anti - fatigue drug, in which levetiracetam is the active ingredient.

[0015] Further, the drug also includes a pharmaceutically acceptable carrier.

[0016] Advantageous Effects

[0017] Through systematic mouse experiments of the present invention, levetiracetam is proved to be able to significantly increase the treadmill running and swimming time of mice. This shows that levetiracetam has a significant effect in enhancing the exercise endurance of the body. For people who need to perform physical activities or exercises for a long time, such as athletes, soldiers, workers, etc., levetiracetam becomes an effective anti - fatigue drug to help them improve their sports performance and work efficiency.

[0018] In the in vitro muscle endurance test, the present invention confirms that levetiracetam significantly improves the fatigue index of mouse muscles. This shows that levetiracetam can directly act on muscle tissues and improve their fatigue state. For people who often perform high - intensity physical activities, levetiracetam helps to reduce muscle fatigue and injury.

[0019] Meanwhile, levetiracetam, as an already marketed drug, its safety and effectiveness have been fully verified. By adding new indications (such as anti-fatigue), it can be quickly applied to new therapeutic fields without going through a long clinical trial process. In addition, levetiracetam has relatively few side effects in the treatment of epilepsy, and the dosage used in the present invention is also lower than its conventional dosage for treating epilepsy. Therefore, when used as an anti-fatigue drug, it is expected that its side effects will also remain at a low level.

[0020] In addition, the current effective treatment means for fatigue in the market are relatively limited, and there are problems such as drug addiction, affecting biological rhythms, and slow onset of action. As a new anti-fatigue drug option, levetiracetam is expected to fill this market gap. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required to be used in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0022] Figure 1 It is a diagram showing the effect of levetiracetam on the treadmill running time of mice in the present invention. Among them, a is the treadmill exercise process of mice, B is the effect of different doses of levetiracetam on the treadmill running time of mice, and C is the effect of different consecutive dosing days on the treadmill running time of mice; Figure 2 It is a diagram showing the effect of levetiracetam on the forced swimming time of mice with load in the present invention. Among them, a is the forced swimming exercise process of mice with load, B is the effect of different doses of levetiracetam on the forced swimming time of mice with load, and C is the effect of different consecutive dosing days on the forced swimming time of mice with load; Figure 3 It is a diagram showing the effect of levetiracetam on the in vitro muscle endurance of mice in the present invention. Among them, a is the muscle endurance situation of mice, and b is the effect of levetiracetam on the in vitro muscle endurance of mice under different electrical stimulation times. DETAILED DESCRIPTION OF THE INVENTION

[0023] Now, various exemplary embodiments of the present invention will be described in detail. This detailed description should not be considered as a limitation of the present invention, but should be understood as a more detailed description of certain aspects, characteristics, and implementation schemes of the present invention.

[0024] It should be understood that the terms used in the present invention are only for describing specific embodiments and are not intended to limit the present invention. Additionally, for the numerical ranges in the present invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Each intermediate value within any stated value or stated range, as well as each smaller range between any other stated value or intermediate value within the stated range, is also included in the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0025] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although the present invention only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials related to the documents. In case of conflict with any incorporated document, the content of this specification shall prevail.

[0026] Without departing from the scope or spirit of the present invention, various improvements and changes can be made to the specific embodiments of the present invention specification, which are obvious to those skilled in the art. Other embodiments obtained from the present invention specification are obvious to those skilled in the art. The present invention specification and examples are merely exemplary.

[0027] Regarding the use of "comprising", "including", "having", "containing", etc. herein, they are all open-ended terms, meaning including but not limited to.

[0028] The test methods used in the following examples are all common experimental methods in the art unless otherwise specified; The test materials used in the following examples are all common experimental materials in the art unless otherwise specified.

[0029] Example 1 Effect of Levetiracetam on the Treadmill Ability of Mice Male C57BL / 6J mice at 8 weeks of age were selected and grouped according to the random principle. First, they were subjected to treadmill training for ten days to learn and adapt to treadmill exercise ( Figure 1a). The slope was set at 10°, the initial speed of the treadmill was 10 m / min, the mice ran for 5 min, and were adapted to electrical stimulation (0.25 mA). Subsequently, the speed was increased by 2.5 m / min every 5 min, with a maximum speed of 15 m / min. The mice were trained for 20 min every day. The treadmill ability of the mice was evaluated in the first three days of training, and the mice with too poor exercise ability were screened out, specifically manifested as the mice hiding in the electrical stimulation area and not running for three consecutive days during training. From the fourth day, the mice with the same exercise ability level were randomly divided into a control group and a drug administration group. The groups with different consecutive drug administration days should complete drug administration on the day before the exhaustion experiment. After ten days of training, the exhaustion experiment of the mice was carried out, and the exhaustion time of the mice was recorded. The environment of the running laboratory was consistent with the feeding conditions, with a temperature of about 22 °C and a relative humidity of 70%. The judgment standard for mouse exhaustion was hiding in the electrical stimulation area, no longer being afraid of electric shock, and remaining motionless on a flat table, with weak limbs and the posterior abdomen completely touching the ground. The time at this moment was recorded for subsequent statistical analysis.

[0030] In the dose - effect experiment, the oral administration doses of levetiracetam were 0, 40, 125, and 375 mg / kg in sequence. The control group was given an equal volume of sterile saline. After continuous administration for 7 days, the treadmill exhaustion time of the mice was detected. In the time - effect experiment, the oral administration dose of levetiracetam was 125 mg / kg, the control group was given an equal volume of sterile saline, and after continuous administration for 0, 1, 3, and 7 days, the treadmill exhaustion time of the mice was detected.

[0031] The results showed that as the administration dose of levetiracetam increased, the running time of the mice showed an increasing trend. When the dose reached 125 mg / kg and 375 mg / kg, the running time of the mice was significantly prolonged. When the oral dose of levetiracetam was 375 mg / kg, the improvement effect was the best, and the running time of the mice was prolonged by about 50% on average ( Figure 1 b). In the time - effect experiment of levetiracetam, the optimal dose of levetiracetam, 375 mg / kg, was selected, and treadmill tests were carried out after administration for 1, 3, and 7 days respectively. As the administration time of levetiracetam prolonged, the treadmill time of the mice gradually prolonged. When continuously administered for 7 days, the prolongation of the treadmill time of the mice was the most significant, and the treadmill time was prolonged by about 50% ( Figure 1 c), significantly improving the muscle endurance of the mice.

[0032] Example 2. Effect of levetiracetam on the swimming ability of mice Eight-week-old male C57BL / 6J mice were selected and first subjected to three days of weightless swimming training to learn and adapt to swimming. Mice that could not swim (i.e., did not paddle with their hind legs) were excluded, and the eligible mice were randomly grouped. They were gavaged with the required dose for 7 consecutive days, and 30-min weightless adaptation training was carried out starting from the fourth day of administration. Two hours after the last administration, a lead wire weighing 5% of the body weight was attached to the root of the mouse's tail, and each mouse was placed separately in a water bucket (46 cm high, 20 cm in diameter) with a water depth of about 25 cm and a water temperature of 24 - 26 °C. When the mouse sank below the water surface and could not return to the water surface by itself, it was considered exhausted. All mice participated in the swimming experiment at the same time on the same day ( Figure 2 a). The time period from the start of swimming to exhaustion was recorded by a stopwatch and was called the swimming time.

[0033] The results showed that as the dose of levetiracetam increased, the weight-bearing swimming time of the mice prolonged. At the doses of 125 mg / kg and 375 mg / kg, the average weight-bearing swimming time of the mice increased significantly ( Figure 2 b). After administering the optimal dose of 375 mg / kg for 1, 3, and 7 days respectively, the swimming time of the mice showed an increasing trend with the increase in the administration time, and it increased significantly after 7 days of administration, significantly improving the muscle endurance of the mice.

[0034] Example 3 Effect of levetiracetam on the in vitro muscle endurance of mice Using the Medlab-4C / 501H biological function signal acquisition and analysis processing system, the isolated gastrocnemius-soleus muscle of the mice was tested for muscle endurance. During this process, first, the distal tendon was fixed to the tension sensor probe with surgical suture, and at the same time, the proximal knee joint area was fixed to the fixing frame to ensure that the whole device was vertical. The distance between the two ends was adjusted to make the muscle tension at the balance point. The balance point was the muscle tension in the initial static state, and after applying the test electrical pulse, the muscle returned to this point. An electrical pulse of 10 V and 5 ms duration was emitted once per second for 3 min. During the test, the tetanic contraction force of the muscle at each stimulation time point was recorded in real time, and the corresponding contraction force curve was generated. The ratio of the muscle tension at that moment to the initial tension was calculated every 20 s. The oral administration dose of levetiracetam was selected as 375 mg / kg, and the muscle fatigue time was evaluated by the above method. The specific results are as Figure 3 shown. The results showed that compared with the control group, after administering 375 mg / kg of levetiracetam, the muscle of the mice showed stronger muscle strength after continuous electrical stimulation for 100 s, and the decline rate of muscle strength was significantly slowed down, indicating that it could significantly improve muscle endurance.

[0035] The above-described embodiments merely represent several implementation manners of the present invention. Their descriptions are relatively specific and detailed, but they should not be construed as limiting the scope of the invention patent. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made, and these all fall within the protection scope of the present invention. Therefore, the protection scope of the present invention patent shall be subject to the appended claims.

Claims

1. Application of levetiracetam in the preparation of anti-fatigue drugs.

2. The use according to claim 1, characterized in that The levetiracetam can enhance the body's exercise endurance and improve its fatigue state.

3. The use according to claim 1, characterized in that The levetiracetam can prolong the time of fatigue caused by continuous muscle contraction.

4. The use according to claim 1, characterized in that The dosage forms of the drug include tablets, capsules, oral preparations and injections.

5. The use according to claim 4, characterized in that: The tablets include coated tablets.

6. The use according to claim 4, characterized in that: The oral preparation includes oral liquid preparation, oral granule preparation and oral powder preparation.

7. The use according to claim 4, characterized in that: The injection includes freeze-dried powder injection and injection emulsion.

8. An anti-fatigue drug, characterized in that: In the medicine, levetiracetam is the active ingredient.

9. The drug according to claim 8, characterized in that The medicament further includes a pharmaceutically acceptable carrier.

Images