KR20220141939A - A composition for relieving and treating epilepsy - Google Patents

Abstract

The present invention relates to a composition for relieving and treating epilepsy-related diseases comprising validamycin A as an active ingredient. It is confirmed that validamycin A has an effect of preventing abnormal brain wave generation and suppressing seizures through brain wave signal test and motility measurement in a fairly low concentration range, and there is no toxicity to embryos within the concentration range, so that the validamycin A can be applied as a candidate drug for epilepsy alleviation and/or treatment.

Description

Composition for alleviating and treating epilepsy comprising validamycin A {A COMPOSITION FOR RELIEVING AND TREATING EPILEPSY}

The present invention relates to a composition for alleviating and treating epilepsy comprising validamycin A.

Epilepsy is a group of chronic diseases in which seizures occur repeatedly because some of the nerve cells generate excessive electricity in a short time. The standardized mortality ratio of patients is 1.3-7.2, which is higher than that of the general population.

Epilepsy is the most common neurological disease, affecting about 0.5% to 1% of the world's population. According to the WHO epilepsy report in 2019, it is estimated that about 50 million people worldwide have epilepsy, and there are about 61 new cases per 100,000 people every year.

In Korea, it is estimated that there are about 300,000 to 400,000 epilepsy patients, and it is reported that about 20,000 new epilepsy patients occur every year.

In addition, it is known that 70% of all epilepsy begins at the age of children and adolescents, and the incidence is particularly high in infancy. The incidence and prevalence are highest within the first year of life, then drop sharply, and show a U-shape that sharply increases again in the elderly over 60 years of age. The prevalence of experiencing seizures during life reaches 10-15%.

Epilepsy is a chronic disease in which epileptic seizures occur repeatedly, and the causes are very diverse, and thus, the exact cause is not known.

However, with the recent development of neuroimaging technology, microscopic pathological changes in the brain that could not be observed in the past can be observed, and the identification of the cause of epilepsy is gradually expanding.

According to the epilepsy epidemiologic survey published by the Korean Epilepsy Society in 2012, more than two-thirds of epilepsy patients are idiopathic or latent with no specific cause, and the remaining cases are serious causes that can be found. In other words, if there is a past history of neuropathological changes or brain damage such as stroke, congenital anomaly, head trauma, encephalitis, brain tumor, degenerative encephalopathy, childbirth injury, central nervous system developmental disorder, and genetic predisposition, epilepsy may be induced. it is known that there is

Treatment of epilepsy can be broadly classified into drug treatment and non-drug treatment, that is, surgery, ketogenic diet, and vagus nerve stimulation.

However, since non-drug treatment is being performed only for patients who are resistant to drugs, drug treatment has been used as the main method for epilepsy treatment.

Conventional drugs include phenytoin (Dilantin®), valproate (Valproate: Orfil®, Depakine®, Depakote®), carbamazepine (Tegretol®), phenobarbital (Phenobarbital: Luminal®), etosuccimide (Ethosuximide: Zarontin®), and more recently topiramate (topamax®), lamotrigine (Lamictal®), vigabatrin (Sabril®), and oxcarbazepine (Oxcarbazepine: Trileptal®). developed and commercialized.

Epilepsy drugs such as valproic acid are also used to treat depression and cognitive decline, and when used by pregnant women, they cause various side effects to the fetus and have minor side effects such as nausea, vomiting and dizziness even within the blood treatment concentration range. In addition to fetal toxicity, it can cause serious side effects such as hepatotoxicity and coma.

Therefore, it is necessary to develop an epilepsy drug that is non-toxic and specific for various causes and seizure symptoms.

Validamycin A is an agricultural antibiotic applied to foods such as grains, fruits, and vegetables, and is classified as a fungicide with the function of inhibiting the growth of pathogenic bacteria.

[Prior Patent Literature]

Republic of Korea Patent Publication No. 10-2016-0113516

The present invention solves the above problems, and has been devised by the above necessity, and an object of the present invention is to provide a novel composition for alleviating and treating epilepsy.

In order to achieve the above object, the present invention provides a composition for alleviating and treating epilepsy comprising validamycin A as an active ingredient.

In an embodiment of the present invention, the effective amount of the validamycin A is preferably 0.1 to 100 μM, and the effective amount of the validamycin A is more preferably 1 μM, but is not limited thereto.

In another embodiment of the present invention, the effective amount of validamycin A is preferably 0.75 mg/kg to 1200 mg/kg based on zebrafish, and the effective amount of validamycin A is 75 mg/kg to 1200 based on zebrafish It is more preferably mg/kg, but is not limited thereto.

In another embodiment of the present invention, the composition is characterized in that it reduces the number of seizures in the subject to be treated, but is not limited thereto.

In another embodiment of the present invention, the composition is characterized in that it reduces the seizure duration of the subject to be treated, but is not limited thereto.

In one embodiment of the present invention, the composition is characterized in that it reduces the average seizure time of the subject to be treated, but is not limited thereto.

In another embodiment of the present invention, the composition is characterized in that it reduces the irregular movement of the subject to be treated, but is not limited thereto.

In a preferred embodiment of the present invention, the composition is characterized in that it prevents abnormal EEG generation of the treatment target, but is not limited thereto.

In addition, in one application example of the present invention, the composition is preferably a pharmaceutical or food composition, but is not limited thereto.

"Epilepticism", a disease to be alleviated or treated by the composition of the present invention, is due to abnormal hyperexcitability and hypersynchronization of the brain, which causes some of the nerve cells to generate excessive electricity in a short period of time, causing repeated seizures. It is a serious neurological disease that involves neurobiological, mental, cognitive, and social changes.

In addition, unlike general neurological diseases in which nerve cells degenerate or die, cognitive impairment, behavioral disorders, etc., epilepsy is characterized in that it is a neurological disease caused by abnormally excessive activation of nerve cells.

In addition, excitotoxicity due to abnormal hyperexcitability of nerve cells is induced, and in the hippocampus, among cerebral regions where pathological damage due to epilepsy is well observed, hippocampal sclerosis, colloidization ( gliosis), abnormal neurogenesis, cytoarchitectural abnormality of dentate granule cells, and abnormal synaptic circuit formation.

As the above-mentioned pathological phenomena in the hippocampus progress, chronic epileptic seizures occur, cognitive and memory impairments, and drug-refractory epilepsy that does not respond to drug treatment occurs.

As used herein, the term “alleviation” refers to any action that at least reduces the severity of a parameter, eg, a symptom, associated with the condition being treated. In this case, the composition may be used before or after the onset of the disease for alleviation of epilepsy, simultaneously or separately with the medicament for treatment.

As used herein, the term “treatment” refers to any action in which the symptoms of epilepsy are improved or beneficially changed by administration of the pharmaceutical composition according to the present invention.

The pharmaceutical composition according to the present invention may include a pharmaceutically acceptable carrier in addition to the active ingredient.

In this case, pharmaceutically acceptable carriers are those commonly used in formulation, and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose. , polyvinyl pyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil. In addition, a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc. may be additionally included in addition to the above components.

The pharmaceutical composition of the present invention may be administered orally or parenterally (eg, intravenously, subcutaneously, intracerebrovascular, intraperitoneally or locally applied) according to a desired method, and the dosage may vary depending on the patient's condition and Although it varies depending on body weight, disease severity, drug form, administration route and time, it may be appropriately selected by those skilled in the art.

The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, “pharmaceutically effective amount” means an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is determined by the type, severity, activity of the drug, and the type of disease in the patient. Sensitivity to the drug, administration time, administration route and excretion rate, duration of treatment, factors including concomitant drugs and other factors well known in the medical field.

The pharmaceutical composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or multiple times.

In consideration of all of the above factors, it is important to administer an amount that can obtain the maximum effect with a minimum amount without side effects, which can be easily determined by those skilled in the art.

Specifically, the effective amount of the pharmaceutical composition of the present invention may vary depending on the patient's age, sex, condition, weight, absorption of the active ingredient into the body, inactivation rate and excretion rate, disease type, and drugs used in combination, in general 0.001 to 500 mg per 1 kg of body weight may be administered daily or every other day, or may be administered in divided doses 1 to 3 times a day.

However, the dosage may be increased or decreased according to the route of administration, the severity of obesity, sex, weight, age, etc., and thus the dosage is not intended to limit the scope of the present invention in any way.

The composition may be prepared in a unit dose form by formulating using a pharmaceutically acceptable carrier and/or excipient according to a method readily practiced by those skilled in the art, or may be prepared by internalizing in a multi-dose container.

In this case, the formulation may be in the form of a solution, suspension, syrup, or emulsion in oil or aqueous medium, or may be in the form of an extract, powder, powder, granule, tablet or capsule, and may additionally include a dispersant or stabilizer.

In addition, the composition may be administered as an individual therapeutic agent or may be administered in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents.

The present invention relates to a food composition for preventing or improving epilepsy.

As used herein, the term "prevention" refers to any action that suppresses or delays the onset of epilepsy by administering the composition according to the present invention.

As used herein, the term “improvement” refers to any action that at least reduces a parameter related to the condition being treated, for example, the severity of symptoms.

In this case, the health functional food composition may be used before or after the onset of the disease in order to prevent or improve epilepsy, simultaneously with or separately from the medicament for treatment.

As used herein, the term "food composition" is one selected from the group consisting of tablets, pills, powders, granules, powders, capsules and liquid formulations, including one or more of carriers, diluents, excipients and additives. characterized.

Foods that can be added to the composition of the present invention include various foods, powders, granules, tablets, capsules, syrups, beverages, gums, tea, vitamin complexes, health functional foods, and the like. Additives that may be further included in the present invention include natural carbohydrates, flavoring agents, nutrients, vitamins, minerals (electrolytes), flavoring agents (synthetic flavoring agents, natural flavoring agents, etc.), coloring agents, fillers, lactic acid and salts thereof, At least one component selected from the group consisting of alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, antioxidants, glycerin, alcohols, carbonation agents and pulp may be used.

Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; disaccharides such as maltose, sucrose and the like; and polysaccharides such as conventional sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the flavoring agent, natural flavoring agents (taumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.

In addition to the above, the composition according to the present invention contains various nutrients, vitamins, minerals (electrolytes), synthetic flavoring agents and flavoring agents such as natural flavoring agents, coloring agents and thickeners, facic acid and salts thereof, alginic acid and salts thereof, organic acids, protection It may contain a sexual colloid thickener, a pH adjuster, a stabilizer, a preservative, glycerin, alcohol, a carbonation agent used in carbonated beverages, and the like.

In addition, the composition according to the present invention may contain the pulp for the production of natural fruit juices and vegetable beverages. These components may be used independently or in combination.

Specific examples of the carrier, excipient, diluent and additive include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, erythritol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium phosphate, calcium silicate , microcrystalline cellulose, polyvinylkyrolidone, cellulose, polyvinylpyrrolidone, methylcellulose, water, sugar syrup, methyl hydroxy benzoate, propyl hydroxy benzoate, talc, magnesium stearate and mineral oil. It is preferable that at least one selected from the group be used.

The food composition may be used together with the ingredients of other conventional food compositions, and may be appropriately used according to a conventional method.

The compound of the present invention may be appropriately determined depending on the intended use (prophylactic, health or therapeutic treatment). In general, when preparing a composition for food, it may be added in an amount of 0.01 to 10 parts by weight, preferably 0.05 to 1 part by weight, based on the raw material of the active ingredient.

However, in the case of long-term ingestion for health and hygiene or health control, the amount may be less than or equal to the above range.

The food composition may be contained in health food for the purpose of preventing or improving epilepsy, and there is no particular limitation on the type thereof.

In addition to the above, the food composition of the present invention may further include a pharmaceutically acceptable additive.

In another aspect of the present invention, the present invention provides a method for treating epilepsy comprising administering the pharmaceutical composition to an individual.

In the present invention, "individual" refers to a subject in need of treatment for a disease, and more specifically, refers to mammals such as human or non-human primates, mice, dogs, cats, horses, and cattle. do.

Hereinafter, the present invention will be described.

In the present invention, the efficacy of Validamycin A as a new drug candidate for epilepsy was confirmed through toxicity and efficacy tests using zebrafish.

In the present invention, it was confirmed that Validamycin A had no embryonic toxicity in a fairly low concentration range, and it was confirmed that validamycin A had the effect of preventing abnormal EEG and suppressing seizures through EEG signal test and motility measurement within this concentration range. did. That is, it was confirmed that it had efficacy as a drug for alleviating the symptoms of epilepsy.

As can be seen from the present invention, it was confirmed that Validamycin A has no embryonic toxicity in a fairly low concentration range, and validamycin A prevents abnormal EEG generation and suppresses seizures through EEG signal test and motility measurement within this concentration range. Validamycin A can be applied as a drug candidate for alleviating epilepsy and/or treatment by confirming that it has the efficacy.

1 is a schematic diagram of zebrafish fry EEG signal measurement;
2 is a schematic diagram of a zebrafish adult brain wave signal measuring device,
Figure 3 is an experimental design for measuring motility when pre-treated with valproate (VPA) or validamycin A (VA) in a zebrafish epilepsy disease model, pentylenetetrazol (PTZ)-induced seizure model;
Figure 4 is a zebrafish epilepsy disease model pentylenetetrazol (PTZ)-induced seizure model valproate (VPA) or validamycin A (VA) when pre-treated EEG signal measurement results as 'Average Number of Seizure-like Events' As the picture shown,
Eight fish per group were used, data were presented as mean±SEM, and statistical significance was verified using one-way ANOVA for statistical analysis.
When the p value was less than 0.05, it was judged that there was a statistically significant difference. At this time, the p-value is indicated by * or # depending on the control group, which means that the DMSO 1% group (vehicle) or the PTZ 20mM group (vehicle+PTZ) was used as a control group to indicate statistical significance.
Figure 5 is a zebrafish epilepsy disease model, pentylenetetrazol (PTZ)-induced seizure model, valproate (VPA) or validamycin A (VA) when pre-treated EEG signal measurement results as 'Total Duration of Seizure-like Events' As the picture shown,
Eight fish per group were used. Data were presented as mean ± SEM, and statistical significance was verified using One-way ANOVA.
When the p value was less than 0.05, it was judged that there was a statistically significant difference. At this time, the p-value is indicated by * or # depending on the control group, which means that the DMSO 1% group (vehicle) or the PTZ 20mM group (vehicle+PTZ) was used as a control group to indicate statistical significance.
Figure 6 is a zebrafish epilepsy disease model pentylenetetrazol (PTZ)-induced seizure model valproate (VPA) or validamycin A (VA) when pre-treated EEG signal measurement results of 'Mean Duration of Seizure-like Events' As the picture shown,
Eight fish per group were used. Data were presented as mean±SEM, and statistical significance was verified using One-way ANOVA for statistical analysis.
When the p value was less than 0.05, it was judged that there was a statistically significant difference. At this time, the p-value is indicated by * or # depending on the control group, which means that the DMSO 1% group (vehicle) or the PTZ 20mM group (vehicle+PTZ) was used as a control group to indicate statistical significance.
7 is a zebrafish epilepsy disease model, pentylenetetrazol (PTZ)-induced seizure model, adult EEG signal measurement results when valproate (VPA) or validamycin A (VA) is treated as 'Average Number of Seizure-like Events' As the picture shown,
Eight or nine fish per group were used. Data were presented as mean ± SEM, and statistical significance was verified using One-way ANOVA.
When the p value was less than 0.05, it was judged that there was a statistically significant difference. At this time, the p-value is indicated by * or # depending on the control group, which means that the DMSO 0.1% group (vehicle) or the PTZ 200mpk group (vehicle+PTZ) was used as a control group to indicate statistical significance.
8 is a zebrafish epilepsy disease model, pentylenetetrazol (PTZ)-induced seizure model, adult EEG signal measurement results when valproate (VPA) or validamycin A (VA) is treated as 'Total Duration of Seizure-like Events' As the picture shown,
Eight fish per group were used. Data were presented as mean ± SEM, and statistical significance was verified using One-way ANOVA for statistical analysis.
When the p value was less than 0.05, it was judged that there was a statistically significant difference. At this time, the p-value is indicated by * or # depending on the control group, which means that the DMSO 0.1% group (vehicle) or the PTZ 200mpk group (vehicle+PTZ) was used as a control group to indicate statistical significance.
9 is a diagram showing the 'Relative angular velocity' of adult motility measurement results when valproate (VPA) or validamycin A (VA) was pretreated in the zebrafish epilepsy disease model, pentylenetetrazol (PTZ)-induced seizure model.
Angular velocity indicates irregular movement. 12-26 fish per group were used. Data were presented as mean ± SEM, and statistical significance was verified using student's t-test for statistical analysis.
When the p value was less than 0.05, it was judged that there was a statistically significant difference.

Hereinafter, the present invention will be described in more detail through non-limiting examples. However, the following examples are intended to illustrate the present invention, and the scope of the present invention is not to be construed as being limited by the following examples.

In the present invention, wild type adult zebrafish were bred at a temperature of 27.5° C. in a light-dark environment with a cycle of 14 hr/10 hr, and zebrafish embryos were obtained by inducing natural spawning, and E3 medium (5 mM NaCl, 0.33 mM MgSO ₄ , 0.33 mM CaCl) ₂ , and 0.17 mM KCl) into a petri dish and bred in an incubator at 28.5°C.

Example 1: Measurement of EEG signals in the zebrafish epilepsy model (see FIG. 1)

The epilepsy disease model used in the present invention was a Pentylenetetrazol (PTZ)-induced seizure model in which zebrafish fry were treated in a Pentylenetetrazol (PTZ) solution.

After fertilization 6-day-old zebrafish fry were treated with antiepileptic drug (AED) for 18 hours, 20 mM PTZ was treated for 15 minutes, and EEG recording was performed for 10 minutes.

After sucking the drug-treated fry from a 96-well plate using an 18 gauge needle, they were placed in an electroencephalography (EEG) recording chamber.

EEG EEG of zebrafish fry was measured using an invasive electrode.

EEG signals were measured and processed using Biopac Systems Inc.'s MP36 instrument.

Example 2: Measurement of adult EEG signals in a zebrafish epilepsy model (see FIG. 2)

The epilepsy disease model used in the present invention was a Pentylenetetrazol (PTZ)-induced seizure model in which Pentylenetetrazol (PTZ) was orally administered (p.o.) to adult zebrafish.

Adult zebrafish were anesthetized in 15 ppm Eugenol bath until anesthesia stage 3 was reached.

The adults were then fixed in the device and 7.5 ppm Eugenol was orally administered to maintain anesthesia out of the water.

Electrodes were non-invasively attached to the head of adult fish to measure brain EEG EEG (see figure in a square in FIG. 2).

After oral administration of the subject epilepsy drug of the present invention and PTZ (220 mg/kg) at the same time, EEG was measured for 20 minutes. To test the efficacy of new drug candidates for epilepsy, zebrafish EEG was measured by attaching electrodes to the head non-invasively.

EEG signals were measured and processed using Biopac Systems Inc.'s MP36 instrument.

Example 3: Measurement of relative angular velocity of adult motility in zebrafish epilepsy model (see FIG. 3)

Adult zebrafish were transferred from the breeding facility to the behavioral laboratory, and an acclimation period of more than 2 hours was performed in a plastic vat filled with 2L system water.

Adult zebrafish were placed in a 90mm petri dish containing the target epilepsy drug of the present invention and treated for 30 minutes.

After adding PTZ to the final concentration of 10 mM, the behavior of adult fish was recorded and observed. The free swimming of the adult fish was recorded using a Sony HDR-CX560 video camera.

Using the recordings, motility was analyzed using the Ethovision XT14.0 program.

The results of the above examples are described below.

Evaluation of Epilepsy Drug Efficacy by EEG Measurement in PTZ Epilepsy Model

EEG signal measurement results in zebrafish epilepsy model

When the zebrafish epilepsy disease model, pentylenetetrazol (PTZ)-induced seizure model, was pretreated with valproate (VPA) or validamycin A (VA), EEG signals were measured to determine whether the epilepsy symptoms could be alleviated in the fry.

As shown in FIG. 4 , when compared with the case of inducing seizures in the 20mM PTZ group, the average number of seizures in all groups except for the VA 0.01μM group showed statistical significance.

In particular, the decrease in the number of seizures was greatest at 1 μM of VA, and at concentrations higher than 1 μM, the number of seizures increased as the concentration increased.

As shown in Figure 5, when compared to the 20 mM PTZ group, VA 0.01 μM. The seizure duration decreased in all groups except 0.1 μM, which was statistically significant. The VPA 1000 μM and VA 1 μM, 10 μM and 100 μM groups showed shorter seizure duration compared to the PTZ 20 mM.

In particular, the decrease in seizure duration is greatest at VA 1 μM, and at a concentration higher than that concentration, the seizure duration rather increases as the concentration increases.

As shown in FIG. 6 , when compared with the 20mM PTZ group, the mean seizure time decreased in the VPA 1000 μM, VA 1 μM, and 10 μM groups, showing statistical significance. The VPA 1000 μM and VA 1 μM, 10 μM, and 100 μM groups showed shorter mean seizure times compared to the PTZ 20 mM.

Combining the research results using the epilepsy model of zebrafish fry as described above,

When analyzed based on three indicators, 'Average Number of Seizure-like Events', 'Total Duration of Seizure-like Events', and 'Mean Duration of Seizure-like Events', which are mainly used in EEG EEG measurement,

Among the VA groups, the efficacy of antiepileptic drugs (AEDs) appeared to appear from the VA concentration of 1 μM or higher,

In particular, the effect was the most excellent at VA 1 μM.

Adult EEG signal measurement results in zebrafish epilepsy model

When valproate (VPA) or validamycin A (VA) was treated in the zebrafish epilepsy model, pentylenetetrazol (PTZ)-induced seizure model, EEG signals were measured to determine whether epilepsy symptoms could be alleviated in adult fish.

As shown in FIG. 7 , when compared with the PTZ Condition, the VPA 248mpk group showed statistical significance in reducing the average number of seizures. In addition, the average number of seizures decreased as the VA dose increased, but at VA 75mpk, the number of seizures had a primary value of the lowest average number of seizures. The mean number of seizures decreased in the VA 600 mpk and VA 1200 mpk groups were statistically significant.

As shown in FIG. 8 , as compared with the PTZ group, the total seizure time decreased as the VA dose increased, but had the lowest primary value of the total seizure time at VA 75mpk, and thereafter, as the dose increased, While the total seizure time increased, there was a statistical significance in the decrease in the total seizure time in the VA 300mpk, VA 600mpk, and VA 1200mpk groups.

Combining the research results using the epilepsy model of adult zebrafish as described above,

When analyzed based on two indicators, 'Average Number of Seizure-like Events' and 'Total Duration of Seizure-like Events', which are mainly used in EEG EEG measurement, appeared to be effective,

In particular, the effect was the most excellent at VA 1200mpk.

Relative angular velocity measurement result of adult motility in zebrafish epilepsy model

When the zebrafish epilepsy model, pentylenetetrazol (PTZ)-induced seizure model, was pretreated with valproate (VPA) or validamycin A (VA), the angular velocity of motility was measured to determine whether seizures could be suppressed in adult fish.

Angular velocity is a factor that identifies irregular movements, that is, seizures. An increase in angular velocity means an increase in irregular movement.

As shown in FIG. 9 , when compared with the PTZ group, the angular velocity was statistically significantly decreased in the VPA 70 μM, VA 1 μM, and VA 100 μM groups. A decrease in the effect seen in the VA 10 μM group compared to the VA 1 μM and VA 100 μM groups was repeatedly observed.

Combining the research results using the epilepsy model of adult zebrafish as described above,

When the angular velocity measurement of adult fish motility was analyzed based on the index of whether seizures could be suppressed, the efficacy of the epilepsy drug (AED) appeared from VA 1 μM,

In particular, the effect was the most excellent in VA 100 μM.

Claims (12)

A composition for alleviating and treating epilepsy comprising validamycin A as an active ingredient. According to claim 1,
The composition for alleviating and treating epilepsy, characterized in that the effective amount of the validamycin A is 0.1 to 100 μM. 3. The method of claim 2,
The composition for alleviating and treating epilepsy, characterized in that the effective amount of the validamycin A is 1 μM. According to claim 1,
The composition for alleviating and treating epilepsy, characterized in that the effective amount of the validamycin A is 0.75 mg/kg to 1200 mg/kg based on zebrafish. 5. The method of claim 4,
The composition for alleviating and treating epilepsy, characterized in that the effective amount of the validamycin A is 75 mg/kg to 1200 mg/kg based on zebrafish. 6. The method of claim 5,
The composition for alleviating and treating epilepsy, characterized in that the effective amount of the validamycin A is 600 mg / kg to 1200 mg / kg based on zebrafish. According to claim 1,
The composition is a composition for alleviating and treating epilepsy, characterized in that it reduces the number of seizures in the subject to be treated. According to claim 1,
The composition is a composition for alleviating and treating epilepsy, characterized in that it reduces the seizure duration of the subject to be treated. According to claim 1,
The composition is a composition for alleviating and treating epilepsy, characterized in that it reduces the average seizure time of the subject to be treated. According to claim 1,
The composition is a composition for alleviating and treating epilepsy, characterized in that it reduces the irregular movement of the subject to be treated. According to claim 1,
The composition is a composition for alleviation and treatment of epilepsy, characterized in that it prevents the abnormal EEG generation of the subject to be treated. According to claim 1,
The composition is a composition for alleviating and treating epilepsy, characterized in that the pharmaceutical or food composition.

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