Use of levetiracetam in preparation of Anti-obesity drug

Abstract

Provided is use of levetiracetam or a pharmaceutically acceptable salt thereof in the preparation of an anti-obesity drug. The pharmaceutically acceptable salt is an acid addition salt formed by levetiracetam and the following acid: hydrochloric acid, hydrobromic acid, sulfuric acid, lactic acid, citric acid, phosphoric acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalene sulfonic acid, tartaric acid, pyruvic acid, acetic acid, maleic acid or succinic acid, fumaric acid, salicylic acid, phenylacetic acid, or mandelic acid. Levetiracetam can significantly inhibit OA-induced obesity in Caenorhabditis elegans and significantly reduce the body weight of C56BL / 6J mice with DIO. Levetiracetam has a significant anti-obesity effect and can be used as an anti-obesity drug.

Description

Application of levetiracetam in preparing weight loss drugs Technical Field

[0001] The present invention belongs to the technical field of drug research and development, and in particular relates to an application of levetiracetam in the preparation of a weight-loss drug. Background Art

[0002] Obesity is a growing global health problem, closely associated with multiple serious health risks, including cardiovascular disease, diabetes, hypertension, certain cancers, and bone and joint problems. The treatment and management of obesity remains an important area of ​​clinical and scientific research. Traditional treatments for obesity include diet, exercise, medication, and surgery. However, some medications and surgical approaches are associated with significant side effects and limitations in synthetic drug synthesis. Therefore, there is a need to discover safer and more effective treatments for obesity. Drug repositioning is an emerging research field that aims to repurpose existing drugs or discover new uses to address the unmet medical needs of various diseases. This approach holds great potential in the field of weight loss drugs, as it could offer a new approach to treating obesity, reducing the time and cost of drug development and the risk of side effects. Several obesity treatments have been developed. These drugs typically reduce weight by suppressing appetite, promoting metabolism, improving energy balance, or affecting food digestion and absorption. However, these drugs are often associated with side effects, drug interactions, and long-term sustainability issues.

[0003] Levetiracetam (CAS No. 102767-28-2) is an antiepileptic drug used to treat epilepsy and epilepsy-related disorders. The structure of levetiracetam is as follows:

[0004] First approved by the FDA in 1999, levetiracetam has become a commonly used first-line treatment in clinical practice. Levetiracetam is currently widely used in clinical practice to treat various types of epileptic seizures, including partial-onset seizures, generalized seizures, and specific types of epilepsy. It is often used in conjunction with other antiepileptic drugs to provide a more comprehensive therapeutic effect. To date, there have been no reports of levetiracetam being used for weight loss in obese individuals.

[0005] Summary of the Invention

[0006] The present invention aims to provide an application of levetiracetam in preparing a weight-loss drug.

[0007] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0008] The present invention provides an application of levetiracetam or a pharmaceutically acceptable salt thereof in the preparation of a weight-loss drug.

[0009] The pharmaceutically acceptable salt is an acid addition salt formed by levetiracetam and the following acids: hydrochloric acid, hydrobromic acid, sulfuric acid, lactic acid, citric acid, phosphoric acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, tartaric acid, pyruvic acid, acetic acid, maleic acid or succinic acid, fumaric acid, salicylic acid, phenylacetic acid or mandelic acid, etc.

[0010] The structure of the levetiracetam is as follows:

[0011] The present invention provides an application of levetiracetam or a pharmaceutically acceptable salt thereof in the preparation of a weight-loss drug, wherein levetiracetam or a pharmaceutically acceptable salt thereof is used as a single active ingredient.

[0012] The present invention also provides a pharmaceutical preparation prepared from levetiracetam or a pharmaceutically acceptable salt thereof, and medically acceptable excipients or other pharmaceutically acceptable ingredients.

[0013] The dosage forms of the pharmaceutical preparations are injections, capsules, tablets, granules, pills, microcapsule preparations, microsphere preparations, nano preparations, etc.

[0014] Due to the adoption of the above technical solution, the present invention has the following advantages and beneficial effects:

[0015] In the animal experiments of the present invention, the use of levetiracetam on Caenorhabditis elegans can significantly inhibit OA-induced obesity in the nematodes; and the use of levetiracetam on C56BL / 6J mice can significantly reduce the body weight of DIO obese mice.

[0016] From the above efficacy test results, it can be seen that levetiracetam has a significant weight loss effect and can be used as a weight loss drug. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] FIG1 is a schematic diagram of the fat content of nematodes in Example 1.

[0018] FIG2 is a schematic diagram showing changes in animal body weight over time in Example 2.

[0019] FIG3 is a schematic diagram of the weight change rate of animals in Example 2. DETAILED DESCRIPTION

[0020] In order to explain the present invention more clearly, the present invention is further described below in conjunction with preferred embodiments. Those skilled in the art should understand that the following specific description is illustrative rather than restrictive and should not be used to limit the scope of protection of the present invention.

[0021] Example 1

[0022] 1.1 Construction of the C. elegans obesity model

[0023] Adding oleic acid (OA) to the diet significantly increases fat accumulation in nematodes. Similarly, using OilRed-O (ORO) staining, the study found that ORO levels were significantly elevated when animals were fed OA compared to OP50 medium, establishing a fat accumulation model (PMID: 35140229).

[0024] 1.2 Experimental instruments

[0025] Electron microscope.

[0026] 1.3 Experimental steps

[0027] C. elegans were fed a HFD until L4 larvae. Synchronized L1 larvae were grown on NGM plates that had been fed the HFD until L4 larvae and then transferred to NGM plates with normal chow. Different drugs were added to OP50 bacterial suspensions and plated together with the suspensions. The blank control group received OP50 suspension; the OA control group received 4 mM OA mixed with the OP50 suspension; and the levetiracetam control group received 4 mM OA mixed with the OP50 suspension and concurrently administered levetiracetam at a dose of 0.3 μM.

[0028] 1.4 Observation indicators

[0029] Oil Red O staining method: Nematodes were fixed in 4% paraformaldehyde solution and gently rocked at room temperature for 1 hour. The fixed nematodes were washed with 1× PBS, resuspended in 60% isopropanol, and incubated at room temperature for 15 minutes. The nematodes were then stained with a saturated ORO staining solution dissolved in 60% isopropanol overnight with rocking. Afterwards, the nematodes were washed twice with 1× PBS 0.01% Triton X-100 to remove excess dye. The nematodes were then mounted on 2% agar plates and imaged using a microscope at ×10 magnification. The same exposure settings were used for all conditions in each experiment.

[0030] 1.5 Experimental Results

[0031] At a concentration of 0.3 μM, levetiracetam had a significant inhibitory effect on OA-induced obesity in nematodes. The results are shown in FIG1 , which is a schematic diagram of nematode fat content.

[0032] Example 2

[0033] 2.1 Construction of DIO obesity model mice

[0034] Twenty-six 8-week-old C56BL / 6J mice weighing 18-22 g (Changzhou Cavens Laboratory Animal Co., Ltd.) were randomly assigned using a random number table, with 5 mice per cage for a total of 6 cages, and fed a high-fat diet for 12 weeks.

[0035] 2.2 Experimental instruments

[0036] Electronic balance.

[0037] 2.3 Experimental steps

[0038] After 12 weeks of feeding, the animals were randomly assigned to three groups and given different drugs for four consecutive weeks. During this period, they continued to have free access to a high-fat diet and water. The blank group (n = 9) received the same volume of saline as the drug group via oral gavage once daily. The levetiracetam group (n = 9) received 125 mg / kg via oral gavage once daily. The active drug liraglutide group (n = 8) received 0.1 mg / kg via subcutaneous injection twice daily.

[0039] 2.4 Observation indicators

[0040] The body weight changes of mice in each group were recorded and weighed every 7 days.

[0041] 2.5 Experimental Results

[0042] The experimental data were plotted and analyzed using GraphPad Prism 9. One-way ANOVA was used for comparisons between groups, with P < 0.05 considered significant.

[0043] The body weight of mice in the 125 mg / kg levetiracetam group decreased significantly after treatment, with a significant difference compared to the blank group. This indicates that 125 mg / kg levetiracetam has a significant effect on weight loss in obese mice. The results are shown in Figures 2 and 3. Figure 2 is a schematic diagram of the changes in animal weight over time. Figure 3 is a schematic diagram of the rate of change in animal weight.

[0044] From the above efficacy test results, it can be seen that levetiracetam has a significant weight loss effect and can be used as a weight loss drug.

[0045] The above description is merely a preferred embodiment of the present invention and does not constitute any form of limitation to the present invention. Although the present invention has been disclosed as above in terms of a preferred embodiment, it is not intended to limit the present invention. Any technician familiar with this patent can make slight changes or modifications to equivalent embodiments using the above technical content without departing from the scope of the technical solution of the present invention. However, any simple modifications, equivalent changes, and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the solution of the present invention.

Claims

1. Use of levetiracetam or a pharmaceutically acceptable salt thereof in the preparation of a weight loss drug.

2. The use of levetiracetam or a pharmaceutically acceptable salt thereof according to claim 1 in the preparation of a weight loss drug, characterized in that: The pharmaceutically acceptable salt is an acid addition salt formed by levetiracetam and the following acids: hydrochloric acid, hydrobromic acid, sulfuric acid, lactic acid, citric acid, phosphoric acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, tartaric acid, pyruvic acid, acetic acid, maleic acid or succinic acid, fumaric acid, salicylic acid, phenylacetic acid or mandelic acid.

3. The use of levetiracetam or a pharmaceutically acceptable salt thereof according to claim 1 in the preparation of a weight loss drug, characterized in that: The structure of the levetiracetam is as follows:

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