Application of benzodifuranone compound in treatment of intractable epilepsy

Abstract

The invention discloses application of a benzodifuranone compound in preparation of medicines for treating intractable epilepsy, and belongs to the technical field of medicines. According to the application, the benzodifuranone compound is used for treating epilepsy for the first time, and particularly a new candidate drug is provided for treatment of intractable epilepsy. In addition, the invention further provides a compound medicine combining the benzodifuranone compound and sodium valproate, and the benzodifuranone compound and the sodium valproate have an obvious synergistic effect in treatment of intractable epilepsy diseases.

Description

technical field

[0001] The invention belongs to the technical field of medicine, and in particular relates to the application of a benzodifuranone compound in the preparation of drugs for treating refractory epilepsy. Background technique

[0002] Epilepsy is a common neurological disease. It is a syndrome of chronic recurrent transient brain dysfunction, characterized by seizures caused by abnormal discharge of brain neurons. Most patients can be well controlled with anti-epileptic drugs (Anti-Epileptic Drugs), but more than 30% of patients are ineffective to the existing anti-epileptic drugs, which is called refractory epilepsy (Refractory Epilepsy, RE). The International League Against Epilepsy defines RE as epilepsy that cannot control the onset of seizures after selecting ≥ 2 tolerable antiepileptic drugs in sufficient doses and courses of treatment to reach an effective concentration in the body. In China, the diagnosis of RE refers to the absence of central nervous s...

Examples

Embodiment 1

[0015] Example 1 Effect test of Aspeterreurone A on cell model of intractable epilepsy

[0016] The hippocampal neurons cultured to the 7th day were randomly divided into normal control group (group C), model group (group M), model+0.1μMAtrA group (AtrA1 group), model+1μMAtrA group (AtrA2 group), model+10μMAtrA group group (AtrA3 group), model+100 μM AtrA group (AtrA4 group). In the normal control group, the medium was changed to normal extracellular fluid for 3 hours and then returned to 2 mL of maintenance medium culture. In the model group, the medium was changed to magnesium-free extracellular fluid after 3 hours of culture and then returned to 2 mL of maintenance medium culture. Magnesium extracellular fluid was cultured for 3 hours and then restored to maintenance medium containing final concentrations of 0.1 μM, 1 μM, 10 μM, and 100 μM Speterreurone A, and the six-well plate was returned to the incubator for 24 hours of further culture.

[0017] Maintenance medium comp...

Embodiment 2

[0022] Example 2: Study on the curative effect of Aspeterreurone A on lithium-pilocarpine refractory epilepsy rats

[0023]Pilocarpine is a muscarinic receptor agonist, which can activate cholinergic neurons and disrupt the balance of glutamate and γ-aminobutyric acid. Lithium chloride can enhance the function of pilocarpine. Temporal lobe epilepsy is the most common treatment-resistant epilepsy, and the lithium-pilocarpine model is often used to study temporal lobe epilepsy. The pathological features of the lithium-pilocarpine model include inflammation, glial cell proliferation, massive loss of neurons, and mossy fiber sprouting, which are similar to the neuropathological features of temporal lobe epilepsy. Therefore, the present invention selects the lithium-pilocarpine rat model for pharmacodynamic experimental research.

[0024] Healthy male SD rats with body weight in the range of 180-220g. After the experiment started, the lithium chloride-pilocarpine hydrochloride r...

technical field

[0001] The invention belongs to the technical field of medicine, and in particular relates to the application of a benzodifuranone compound in the preparation of drugs for treating refractory epilepsy. Background technique

[0002] Epilepsy is a common neurological disease. It is a syndrome of chronic recurrent transient brain dysfunction, characterized by seizures caused by abnormal discharge of brain neurons. Most patients can be well controlled with anti-epileptic drugs (Anti-Epileptic Drugs), but more than 30% of patients are ineffective to the existing anti-epileptic drugs, which is called refractory epilepsy (Refractory Epilepsy, RE). The International League Against Epilepsy defines RE as epilepsy that cannot control the onset of seizures after selecting ≥ 2 tolerable antiepileptic drugs in sufficient doses and courses of treatment to reach an effective concentration in the body. In China, the diagnosis of RE refers to the absence of central nervous s...

Examples

Embodiment 1

[0015] Example 1 Effect test of Aspeterreurone A on cell model of intractable epilepsy

[0016] The hippocampal neurons cultured to the 7th day were randomly divided into normal control group (group C), model group (group M), model+0.1μMAtrA group (AtrA1 group), model+1μMAtrA group (AtrA2 group), model+10μMAtrA group group (AtrA3 group), model+100 μM AtrA group (AtrA4 group). In the normal control group, the medium was changed to normal extracellular fluid for 3 hours and then returned to 2 mL of maintenance medium culture. In the model group, the medium was changed to magnesium-free extracellular fluid after 3 hours of culture and then returned to 2 mL of maintenance medium culture. Magnesium extracellular fluid was cultured for 3 hours and then restored to maintenance medium containing final concentrations of 0.1 μM, 1 μM, 10 μM, and 100 μM Speterreurone A, and the six-well plate was returned to the incubator for 24 hours of further culture.

[0017] Maintenance medium comp...

Embodiment 2

[0022] Example 2: Study on the curative effect of Aspeterreurone A on lithium-pilocarpine refractory epilepsy rats

[0023]Pilocarpine is a muscarinic receptor agonist, which can activate cholinergic neurons and disrupt the balance of glutamate and γ-aminobutyric acid. Lithium chloride can enhance the function of pilocarpine. Temporal lobe epilepsy is the most common treatment-resistant epilepsy, and the lithium-pilocarpine model is often used to study temporal lobe epilepsy. The pathological features of the lithium-pilocarpine model include inflammation, glial cell proliferation, massive loss of neurons, and mossy fiber sprouting, which are similar to the neuropathological features of temporal lobe epilepsy. Therefore, the present invention selects the lithium-pilocarpine rat model for pharmacodynamic experimental research.

[0024] Healthy male SD rats with body weight in the range of 180-220g. After the experiment started, the lithium chloride-pilocarpine hydrochloride r...

Images