CN117771240A - Application of levetiracetam in preparation of weight-losing medicines - Google Patents
Application of levetiracetam in preparation of weight-losing medicines Download PDFInfo
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- CN117771240A CN117771240A CN202311652436.4A CN202311652436A CN117771240A CN 117771240 A CN117771240 A CN 117771240A CN 202311652436 A CN202311652436 A CN 202311652436A CN 117771240 A CN117771240 A CN 117771240A
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- levetiracetam
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- 229960004002 levetiracetam Drugs 0.000 title claims abstract description 32
- 239000003814 drug Substances 0.000 title claims abstract description 26
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- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 8
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an application of levetiracetam or a medicinal salt thereof in preparing a weight-losing medicament. The pharmaceutically acceptable salt is an acid addition salt of levetiracetam with 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. The animal experiment of the invention can obviously inhibit OA-induced nematode obesity by using levetiracetam on caenorhabditis elegans; the use of levetiracetam on C56BL/6J mice significantly reduced the body weight of DIO obese mice. The result of the drug effect experiment shows that levetiracetam has remarkable weight-losing effect and can be used as a weight-losing drug.
Description
Technical Field
The invention belongs to the technical field of drug development, and particularly relates to an application of levetiracetam in preparation of weight-losing drugs.
Background
Obesity is an increasing health problem worldwide, being closely related to a number of serious health risks, including cardiovascular disease, diabetes, hypertension, certain cancers, and bone joint problems. Treatment and management of obesity has long been an important area of clinical and scientific research. Traditional methods of obesity treatment include diet control, physical exercise, medication, surgery, and the like. However, some drug therapies and surgical approaches are accompanied by non-negligible side effects and limitations of synthetic drugs. Thus, there is a need to find safer, more effective treatments for obesity. Drug repositioning discovery is an emerging field of research aimed at reusing existing drugs or finding new uses to meet the therapeutic needs of different diseases. This approach has great potential in the area of weight loss medicine because it can provide a new approach to treating obesity, reduce the time and cost of drug development, and reduce the risk of side effects. In the prior art, several obesity treatment drugs have been developed. These drugs generally reduce body weight by suppressing appetite, promoting metabolism, improving energy balance, or affecting mechanisms such as food digestion and absorption. However, these drugs are often associated with side effects, drug interactions and sustainability issues for long term use.
Levetiracetam (CAS number 102767-28-2) is an antiepileptic drug for the treatment of epilepsy and epilepsy-related disorders. The structure of levetiracetam is as follows:
it was first approved by the FDA in 1999 and has become one of the first line of therapeutic agents commonly used clinically. Levetiracetam has been widely used clinically at present for the treatment of various types of seizures, including partial seizures, systemic seizures, and special kinds of epileptic symptoms, often with other antiepileptic drugs to provide a more comprehensive therapeutic effect. No report on the weight loss of the obese people by using levetiracetam is known up to the present.
Disclosure of Invention
The invention aims to provide an application of levetiracetam in preparing a weight-losing medicament.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
the invention provides an application of levetiracetam or a medicinal salt thereof in preparing a weight-losing medicament.
The pharmaceutically acceptable salt is an acid addition salt of levetiracetam with 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, and the like.
The structure of levetiracetam is as follows:
the invention provides an application of levetiracetam or medicinal salt thereof in preparing a weight-losing medicament, wherein the levetiracetam or the medicinal salt thereof is taken as a single active ingredient in the application.
The invention also provides a pharmaceutical preparation prepared from levetiracetam or the pharmaceutical salt thereof, and pharmaceutically acceptable auxiliary materials or other pharmaceutically acceptable components.
The dosage forms of the pharmaceutical preparation are injection, capsule, tablet, granule, pill, microcapsule preparation, microsphere preparation, nanometer preparation and the like.
By adopting the technical scheme, the invention has the following advantages and beneficial effects:
the animal experiment of the invention can obviously inhibit OA-induced nematode obesity by using levetiracetam on caenorhabditis elegans; the use of levetiracetam on C56BL/6J mice significantly reduced the body weight of DIO obese mice.
The result of the drug effect experiment shows that levetiracetam has remarkable weight-losing effect and can be used as a weight-losing drug.
Drawings
FIG. 1 is a schematic representation of nematode fat content of example 1.
Figure 2 is a graphical representation of animal body weight as a function of time for example 2.
FIG. 3 is a graph showing the rate of change of body weight of animals in example 2.
Detailed Description
In order to more clearly illustrate the present invention, the present invention will be further described with reference to preferred embodiments. It is to be understood by persons skilled in the art that the following detailed description is illustrative and not restrictive, and that this invention is not limited to the details given herein.
Example 1
1.1 construction of nematode obesity model
The addition of Oleic Acid (OA) to food can significantly increase the fat accumulation of nematodes. Also, by using OilRed-O (ORO) staining, it was found that the ORO level was significantly elevated when animals were fed with OA as compared to OP50 medium, based on which a fat accumulation model (PMID: 35140229) was established.
1.2 laboratory apparatus
An electron microscope.
1.3 Experimental procedure
Caenorhabditis elegans is fed with HFD to L4 larvae, synchronized L1 larvae are grown on NGM plates fed with HFD to L4 larvae, and then transferred to NGM plates with normal diet. And (5) respectively adding different medicines into the OP50 bacterial liquid, and coating the medicines and the bacterial liquid on a plate. Blank group: OP50 bacterial liquid; OA group: mixing 4mM OA with OP50 bacterial liquid; levetiracetam group: 4mM OA was mixed with OP50 bacteria solution and levetiracetam was given at a dose of 0.3. Mu.M.
1.4 observations index
Oil red O staining method: nematodes were fixed in 4% paraformaldehyde solution and gently shaken at room temperature for 1 hour. The immobilized nematodes were washed with 1 XPBS, resuspended in 60% isopropanol and incubated for 15 min at room temperature. Then incubated with saturated ORO staining solution in 60% isopropanol with shaking and nematode staining overnight. Thereafter, the nematodes were washed twice with 1 XPBS 0.01% Triton X-100 to remove excess dye. The nematodes were then fixed on 2% agar plates and imaged with a microscope at x 10 magnification. All conditions in each experiment used the same exposure settings.
1.5 experimental results
Levetiracetam has a remarkable inhibitory effect on OA-induced nematode obesity at a concentration of 0.3 μm, and the results are shown in fig. 1, and fig. 1 is a schematic diagram of nematode fat content.
Example 2
2.1 construction of DiO obese model mice
26 mice (C56 BL/6J, kwangsi laboratory animals Co., ltd.) of 18-22 g at 8 weeks of age were prepared, randomly distributed using a random number table according to a random distribution principle, and 6 cages were used per cage, and the diet was fed for 12 weeks.
2.2 laboratory apparatus
An electronic balance.
2.3 Experimental procedure
After 12 weeks of feeding, the animals were randomly assigned again according to the random number method and divided into 3 groups, and different drugs were administered according to the experimental schedule for 4 consecutive weeks, during which time free high-fat diet and water intake were continued. Blank (n=9): administration by gastric lavage is carried out once a day, and physiological saline with the same volume as the administration group is administered; levetiracetam group (n=9): the medicine is administrated by stomach irrigation once a day, and the dosage is 125mg/kg; positive drug liraglutide group (n=8): subcutaneous injections are given twice daily at a dose of 0.1mg/kg.
2.4 observations index
The weight change of each group of mice was recorded and weighed once every 7 days.
2.5 experimental results
Experimental data were plotted and analyzed using software GraphPad Prism 9. The comparison between groups was significantly different from P <0.05 using One-Way ANOVA analysis.
The significant weight loss of mice treated with levetiracetam at a dose of 125mg/kg was significantly different from that of the blank group, which indicates that levetiracetam has a significant effect on weight loss of obese mice at a dose of 125mg/kg, and the results are shown in fig. 2 and 3, and fig. 2 is a graph showing the change of animal weight with time. FIG. 3 is a graph showing the rate of change of animal body weight.
The result of the drug effect experiment shows that levetiracetam has remarkable weight-losing effect and can be used as a weight-losing drug.
The foregoing description is only illustrative of the preferred embodiment of the present invention, and is not to be construed as limiting the invention, but is to be construed as limiting the invention to any and all simple modifications, equivalent variations and adaptations of the embodiments described above, which are within the scope of the invention, may be made by those skilled in the art without departing from the scope of the invention.
Claims (3)
1. Application of levetiracetam or pharmaceutically acceptable salt thereof in preparing weight-reducing medicine is provided.
2. Use of levetiracetam or a pharmaceutically acceptable salt thereof as claimed in claim 1 for the manufacture of a medicament for reducing weight, wherein the pharmaceutically acceptable salt is an acid addition salt of levetiracetam with: 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. Use of levetiracetam or a pharmaceutically acceptable salt thereof as claimed in claim 1 for the manufacture of a medicament for reducing weight, characterized in that the structure of levetiracetam is as follows:
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2023
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