Application of dipeptidyl peptidase IV (DPP4) inhibitors to preparation of drugs used for preventing and treating epilepsy

A dipeptidyl peptidase and inhibitor technology, which is applied in the field of medical applications to achieve the effects of less toxic and side effects, extremely high toxic and side effects, and long duration of drug efficacy

Inactive Publication Date: 2017-09-29
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there are no relevant reports on the application of DPP4 inhibitors in the prevention and treatment of epilepsy

Method used

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  • Application of dipeptidyl peptidase IV (DPP4) inhibitors to preparation of drugs used for preventing and treating epilepsy
  • Application of dipeptidyl peptidase IV (DPP4) inhibitors to preparation of drugs used for preventing and treating epilepsy
  • Application of dipeptidyl peptidase IV (DPP4) inhibitors to preparation of drugs used for preventing and treating epilepsy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] [Example 1] Studying the effect of DPP4 inhibitors on the behavior of epileptic rats

[0034] Select 30 (220±20g) male SD rats and randomly divide them into 3 groups: control group, epilepsy group and sitagliptin phosphate treatment group. Control group: intraperitoneal injection of normal saline at 35 mg / kg; epilepsy group: intraperitoneal injection of PTZ at 35 mg / kg to construct an epilepsy model; treatment group: intraperitoneal injection of sitagliptin phosphate at 10 mg / kg 20 minutes in advance, and 35 mg / kg 20 minutes later The epilepsy model was established by intraperitoneal injection of PTZ at kg. According to the Racine grading standard (1972), the grades of epileptic seizures are graded from 0 to V. The main manifestations are: grade 0 is normal (no convulsions); Grade II rhythmic nodding and chewing; Grade III unilateral forelimb spasm; Grade IV generalized tonic-clonic convulsions with standing, falling, and retreating; Grade V recurrent generalized tonic...

Embodiment 2

[0036] [Example 2] Studying the effects of DPP4 inhibitors on neuronal discharge in epileptic rats

[0037] In a quiet environment at room temperature, SD rats were injected intraperitoneally with 10% chloral hydrate (0.3mL / 100g) in a state of general anesthesia, and a small hand drill with a diameter of 0.5mm was used to place them 4mm behind the anterior bregma and 4mm on both sides of the midline. Two recording electrode holes were drilled in the skull of the rat, and one reference electrode hole was drilled above the sinuses of the rat. Two insulated stainless steel electrodes were respectively placed in the reference electrode hole and the recording electrode hole on the right, and then all the electrodes were fixed on the rat skull with dental cement (pay attention to aseptic operation during the above operation). Connect the electrode leads to the digital EEG machine, adjust the EEG parameters, and record the discharge of neurons in each group of rats.

[0038] The exp...

Embodiment 3

[0039] [Example 3] Studying the Effect of DPP4 Inhibitors on the Survival Rate of Neurons in Epilepsy Rats

[0040] The main steps are as follows:

[0041] (1) Tissue section: 24 hours after the epileptic behavior observation of SD rats, 10% chloral hydrate (0.3mL / 100g) was injected intraperitoneally to make the rats under general anesthesia, and the left ventricle was perfused and fixed with 4% paraformaldehyde. During the perfusion process, the muscles of the whole body of the rat can be observed to vibrate, and gradually become stiff and rigid. At this time, the brain is decapitated, and then the tissue is paraffin-embedded and sectioned for later use.

[0042](2) Nissl staining: wash the sections sequentially in xylene I 15 min-xylene II 15 min absolute ethanol I 5 min-absolute ethanol II 5 min-85% alcohol 5 min-75% alcohol 5 min-distilled water. The paraffin sections were stained in buffered methylene blue staining solution for 10 min. Differentiate in 0.2 mol / L acetate...

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Abstract

The invention discloses application of DPP4 inhibitors to preparation of drugs used for preventing and treating epilepsy, belonging to the field of medical application. The DPP4 inhibitors are applied to prolong the incubation period of epilepsy of rats, shorten duration time of epilepsy, reduce the grade of attack, lower the amplitude and frequency of abnormal discharge of nerve cells, alleviate neuronal damage of rats with epilepsy, improve neuronal apoptosis of rats with epilepsy, and decrease neuronal degeneration and necrosis of rats with epilepsy. The DPP4 inhibitors in the invention are approved clinical medicines; and the DPP4 inhibitors are definite in active ingredients and curative effect, low in toxic and side effect and long in duration time of drug effect and can reduce cost for research and development of the drugs.

Description

technical field [0001] The invention belongs to the technical field of medical application, and in particular relates to the application of a dipeptidyl peptidase IV (Dipeptidylpeptidase-4, DPP4) inhibitor in the prevention and treatment of epilepsy. Background technique [0002] Epilepsy, commonly known as "shorn horn" or "epilepsy", is a common neurological disease in which the sudden abnormal discharge of brain neurons leads to brain dysfunction. There are about 9 million epilepsy patients in China, and about 400,000 new epilepsy patients are added every year. Epilepsy has become the second most common disease in neurology after headache. [0003] The pathogenesis of epilepsy is very complex and has not been fully elucidated so far. Recurrent seizures of epilepsy have caused great harm to patients, their families, and the society. Treatment methods have gradually expanded from traditional drug therapy to surgery, gene therapy, cell transplantation, and nerve stimulation....

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K31/4985A61K31/40A61K31/403A61K31/513A61K31/522A61P25/08
Inventor 何小华韩松尹君刘云丽张玉松徐健彭碧文刘万红余方
Owner WUHAN UNIV
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