JP2003012513A - Prophylactic and remedy for epilepsy - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a prophylactic and remedy for epilepsy, scarcely causing side effects but highly effective. SOLUTION: This prophylactic and remedy for epilepsy contains at least one compound of theanine and its derivative as an active ingredient. L-theanine, D-theanine, and the derivative of which the base structure is derived therefrom are preferably used as the theanine and its derivative. Appearance of after discharge (AD) or evolution thereof is prevented by administering the theanine. Especially, appearance of AD-like abnormal discharge or evolution thereof is prevented, when the theanine is administered to a patient who lapses into a state that abnormal discharge of the AD is easily caused in the brain by troubles in the childbirth or injuries on the head. Further, sequential epilepsy which is thought to be a secondary disease and accompanies convulsion is prevented.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a prophylactic and therapeutic agent for epilepsy, which is used as a prophylactic and therapeutic agent for "epilepsy" whose main symptom is seizure due to excessive firing of cerebral nerve cells.

[0002]

2. Description of the Related Art "Epilepsy" is defined by the WHO (World Health Organization) as "a chronic brain disorder caused by various etiologies, resulting in repeated firing of cerebral neurons. Sexual seizures (epileptic seizures) are the main features, which are accompanied by various clinical symptoms and laboratory findings. " The epileptic seizure symptoms may take various forms such as consciousness disorder, convulsions, automatosis, etc., depending on the onset site of the sudden cerebral rhythm abnormality and its spread. In addition, epilepsy is not only epileptic seizures, but also periodic dysphoria, interstitial mental disorder, personality change, and intellectual disability are often seen.

Antiepileptic agents typified by barbital compounds such as phenobarbital and benzodiazepine clonazepam and valvalic acid are currently used for the treatment of suppressing such "epileptic seizures". % It is said that seizures are completely suppressed by drug administration.

However, these antiepileptic agents currently used are extremely effective in suppressing seizures, but on the other hand, they have many side effects. For example, central nervous system depression, cardiovascular collapse, aplastic anemia, hallucinations, congestive heart failure, ataxia, personality changes, psychosis, aggressive behavior,
Side effects such as dizziness and sedative effects have been reported, and the development of antiepileptic drugs without side effects has been awaited.

[0005]

Therefore, as a result of intensive studies on a compound having few side effects and having a preventive or therapeutic effect on epilepsy, the present inventor found that theanine, which is one of the amino acids contained in tea etc. The present invention has been made based on the finding that it has an epilepsy preventive and therapeutic action. Specifically, the inventors have found that administration of theanine to epilepsy model rats has an epileptic seizure-suppressing effect, and have arrived at the present invention based on such findings.

That is, the present invention embodies an antiepileptic agent and a therapeutic agent containing or prescribing at least one or more of theanine and its derivative as an active ingredient. In addition to being able to obtain an excellent epileptic preventive effect and therapeutic effect, it has the characteristic of fewer side effects. Theanine is a substance that is routinely ingested through tea, and is now approved as a food additive, and it is certain that it has few side effects.

The disease "epilepsy" is not a single disease but a general term for several disease units whose main symptoms are seizures due to excessive firing of cerebral nerve cells. According to the international classification of epilepsy by seizure type, it can be broadly divided into partial seizures and total seizures, and the former partial seizures can be further divided into simple partial seizures, complex partial seizures, and generalized secondary sex. Yes, the latter generalized seizures are even more seizure-free,
It can be divided into myoclonic seizures, clonic seizures, tonic seizures, tonic-clonic seizures, and weakness seizures. On the other hand, when epilepsy is classified according to the cause, it can be divided into an organic cause having an abnormality such as a brain injury and a functional cause not having the abnormality.The former organic cause is head trauma at delivery, Inborn errors of metabolism, congenital malformations, ischemia in infancy, infectious diseases, degenerative diseases, brain tumors, cerebrovascular disorders, etc. can be mentioned, and the functional cause of the latter is called idiopathic epilepsy And those in which a gene change is observed. The antiepileptic agent and therapeutic agent of the present invention can be expected to have preventive and therapeutic effects on all epileptic epilepsy (partial seizures and total seizures). Also,
It can be expected to have preventive and therapeutic effects on epilepsy (organic and functional causes) of all causes, but is particularly effective against temporal lobe epilepsy (psychomotor seizure).

Regarding the physiological function of theanine, various studies have been conducted on the action on the central nervous system from before. For example, in Japanese Patent Laid-Open No. 9-286727,
It was found that when theanine is administered to cultured nerve cells, it has an effect of suppressing the toxicity of glutamate and an effect of shielding glutamate receptors. "It is characterized by a glutamate antagonist and glutamate receptor-shielding agents containing theanine as an active ingredient. "A preventive agent for neuronal cell death" is disclosed.
Further, in Japanese Patent Laid-Open No. 2000-229854, it was found that when theanine is administered to transient cerebral ischemic gerbils, it has a protective effect on ischemic delayed neuronal cell death. Intraventricular administration agents, intracerebroventricular administration agents for treating / preventing vascular dementia, and intracranial surgery administration agents "are disclosed. However, there is no disclosure about the antiepileptic and therapeutic effects of theanine and its derivatives.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, embodiments of the components, dosage forms, methods of use, etc. of the antiepileptic agent and therapeutic agent of the present invention will be specifically described.

The antiepileptic agent and therapeutic agent of the present invention can be prepared by containing or prescribing at least one or more of theanine and its derivative as an active ingredient.

Theanine and its derivatives include L-glutamic acid-γ-ethylamide (L-theanine) and L-
Glutamic acid-γ-methylamide, D-glutamic acid-
γ-ethylamide (D-theanine), D-glutamic acid-γ-methylamide and other L- or D-glutamic acid-
γ-alkylamide, L- or D-glutamic acid-γ
-A derivative containing an alkylamide in the basic structure (for example, L-
Alternatively, one kind of compound selected from the group consisting of D-glutamic acid-γ-alkylamide glycosides or the like) or a mixture of two or more kinds of compounds can be used.
Among them, L-theanine is particularly preferable because it can be obtained from natural products and is recognized as a food additive, and is easily available and safe.

Theanine and its derivatives can be obtained by various known methods.
Specifically, it can be biosynthesized by a culture method of plants or microorganisms, extracted from tea leaves, or fermented or chemically synthesized. For example, for industrial synthesis, L-pyrrolidonecarboxylic acid obtained by heating L-glutamic acid is converted into a copper salt, which is then reacted with anhydrous ethylamine and finally decopperized to obtain the compound.

In the present invention, theanine and its derivatives can be used alone or in a mixture with other active ingredients. When used alone, for example, theanine can be prepared by dissolving it in purified water, physiological saline, etc. in the form of a purified product, a crudely purified product, or a tea extract. When mixed with other active ingredients, for example, barbital-type compounds such as phenobarbital, benzodiazepine-type clonazepam, and valbroic acid, which are used as active ingredients in antiepileptic agents, and treatment of epilepsy such as docosahexaenoic acid. Also, any of the ingredients known to have a preventive effect, or two or more kinds of these ingredients can be added to the theanine aqueous solution and prepared by a known method before use.

The preventive and therapeutic agents for epilepsy of the present invention are orally or parenterally (for intramuscular injection, intravenous injection,
Subcutaneous administration, rectal administration, transdermal administration, nasal administration, intracerebroventricular administration, etc.) and the like. Above all, it has been found that when it is used as an intraventricular agent, it has an excellent effect, particularly an effect of suppressing induced post-emission (“AD”). In addition to pharmaceuticals, it can be used in various ways as quasi-drugs, cosmetics, health drinks (cans, PET bottles, bottled drinks, etc.), health foods, food additives and the like.

As a usage form, it may be dried by freeze-drying or spray-drying to be provided as a dry powder.
Liquids, tablets, powders, granules, dragees, capsules, suspensions,
It can also be provided as an emulsion, ampoule, injection or the like. When provided as a drug, for example, theanine can be directly dissolved in purified water or physiological saline to prepare it for intracerebroventricular administration. Further, by preparing it as a quasi-drug and making it into a drinkable form such as a bottled drink, a tablet, a capsule, a granule or the like, it is possible to provide a preventive agent that is easy to take. Further, as a health food or a health drink, for example, the active ingredient of the present invention is a milk component, carbonic acid, an excipient (including a granulating agent), a diluent, or a sweetener, a flavor, flour, starch, sugar, oils and fats. A mixture of one or more selected from various proteins such as sugars, raw materials for carbohydrates, vitamins, minerals, etc., for example, sports drinks, fruit drinks, milk drinks, tea drinks, vegetable juices, milk drinks, alcoholic drinks, jellies , Jelly drinks,
It can be provided as a variety of foods and drinks such as carbonated drinks, chewing gum, chocolate, candy, biscuits, snacks, breads, dairy products, fish meat paste products, meat products, frozen desserts, dried foods and supplements.

Although the content of the active ingredient in the present invention varies depending on the use, it is 0.1 in terms of dry weight.
001 to 90% by weight, particularly 0.01 to 90% by weight is preferable. For example, if the active ingredient of the present invention is 0.0
It is mixed at a concentration of 1 to 1% by weight, and flavoring agents, sweeteners, preservatives, etc. are added to this, and packed in 100 ml brown bottle containers to be commercialized as health foods, foods for specified health uses, foods and drinks with special nutrition. be able to. Also, in tablets or capsules,
It can be blended at a concentration of 1 to 90% by weight per tablet or capsule and commercialized as a drug. The theanine and derivative intake is about 0.05-2000 mg / kg.
The day is preferable, and 0.2 to 1000 mg / kg · day is more preferable.

The effects of the present invention will be described in detail below based on experiments.

[Experiment 1] In this experiment, after the firing of an electric kindling model using an experimental animal (After Discharg
e, hereinafter abbreviated as "AD". ) The inhibitory effect of theanine on the appearance, especially the effect of intravenous administration of theanine was examined.

At this time, if the development of AD appearing after electrical stimulation is suppressed, it can be judged that it has a suppressive effect on the construction and expansion of the epileptic neural circuit. The electric kindling model acquires seizure readiness by repeatedly electrically stimulating a part of the brain under a seizure threshold. The seizure readiness of the electric kindling model is introduced by an increase in excitability of nerve cells by excitatory transmitters released from the nerve cell population by electrical stimulation. Repeated electrical stimulation below the stimulation threshold changes the excitability of a wide range of neurons that are in communication with the stimulator via the synapse and lowers the seizure threshold, making it an excellent generalized secondary model. ing. Further, when stimulation is repeated from the start of stimulation to the time when seizure readiness is acquired, the amplitude of AD, which is hyperexcitation of the nerve cell group, increases, and its duration also slightly increases.

(Preparation of Specimen Animal) 10-week-old Wista
Eight male r rats were preliminarily bred for one week, and those having a body weight of 280 g or more were subjected to brain electrode implantation surgery under pentobarbital anesthesia (50 mg / kg, intraperitoneal administration). At this time, the electrode implantation sites were on the CA1 region on both sides of the hippocampus and on the frontal lobe dura mater, a concentric bipolar deep electrode made of stainless steel was used for the former hippocampus, and a stainless screw type electrode was used on the latter dura. 6 for each electrode
It was introduced into a polar microconnector and fixed on the skull with dental cement. In order to prevent infection, a sulfa drug was included in the incision at the time of suturing, and 3,000 units of a penicillin G potassium solution was intramuscularly administered for 5 days after the operation.

After the operation of implanting the electrodes, the animals 10 days or more have been moved into a shield box, and an isolator (SS-201J, Nihon Kohden) was placed in the CA1 region of the right hippocampus with an electric stimulator (SEN-7203, Nihon Kohden). A short wave stimulus with a frequency of 60 Hz and a duration of 1 second was applied through The electrical stimulation was given exactly once a day at 24 hour intervals, the energization amount on the first day was set to 100 μA, the energization amount was increased by 50 μA until the spike of AD appeared, and the AD induction threshold value was determined. After the AD induction threshold is determined, it is 2 according to the AD induction threshold
Specimen animals in which induction of AD was observed for 3 consecutive days by stimulation at 4-hour intervals were used for the experiment.

(Recording system) EEG (cortex,
The hippocampus on the opposite side of the stimulus was derived by wire, amplified by a bioelectric amplifier (AB621G, Nihon Kohden), and then recorded and stored on a magneto-optical disk at a sampling frequency of 200 Hz. Recording conditions: time constant 0.1 sec, high cutoff frequency 6
0 Hz, attenuation characteristic 24 dB / oct, 1 minute before stimulation, 2 minutes after stimulation, total 3 minutes. Moreover, in order to observe the reaction of the animal before and after the stimulation, the image by the CCD camera attached to the measurement box was recorded simultaneously with the electroencephalogram using a digital video recorder.

(Administration Method and Analysis) Group A: L-theanine 0 μmol / kg (control) Group B: L-theanine 100 μmol / kg Group C: L-theanine 2000 μmol / kg Group D: MK801 50 μmol / kg The effect of administration of theanine or MK801 (dizocilpine), which is said to have an antiepileptic effect on AD induction, was examined for the 4 groups.

The administration method was to administer to the tail vein with a constant volume (0.5 ml), and 15 minutes after the administration, an AD-induced threshold stimulus was given to the CA1 region of the right hippocampus by the system similar to that used for the preparation of the specimen animals, and 1 EEG was recorded for 1 minute and 2 minutes after stimulation. Three
With a washout period of one day, administration of the same concentration was performed three times in total. The presence or absence of AD induction was confirmed from the recorded electroencephalogram, and the average amplitude (average maximum amplitude) of 10 discharges with large amplitude as shown in FIG. 1 and the AD duration as shown in FIG. 2 were measured. The mean maximum amplitude and duration of AD were tested for significant difference by the Kruskal-Wallis test. Also, A
Chi-square test was used for the presence or absence of D induction.

(Results) The results of the AD average maximum amplitude are shown in FIGS. 3 and 4. The C group (theanine 2000 μmol / kg administration group) showed significantly lower values in both the frontal cortex and the hippocampus on the opposite side of stimulation than the A group (control group) (p <0.05, p <0.01, respectively). ). As shown in FIGS. 5 and 6, the AD duration was significantly shortened in group C in both the frontal lobe cortex and the hippocampus contralateral to stimulation as compared with group A (p <0.05 in both cases). It is also clear that in any case, the effect of the group C (mmol / kg order) is more remarkable than that of the group B (100 μmol / kg order).

Table 1 below shows A in each group in the frontal cortex.
The number of times that D was induced and the number of times that AD was not induced were shown, and Table 2 shows the significant difference from other groups in that case. Table 3 shows the number of times AD was induced and the number of times AD was not induced in each group in the contralateral hippocampus.
Shows a significant difference from other groups in that case. In addition,
The numerical values in Table 2 and Table 4 indicate the significance level.

[0027]

[Table 1]

[0028]

[Table 2]

[0029]

[Table 3]

[0030]

[Table 4]

Regarding the propagation of AD, in A group (control group) and D group (MK801 administration group), AD is always induced in both the frontal lobe cortex and the hippocampus on the contralateral side with the same stimulation as when the sample animal was prepared. However, in some cases, AD was not induced when the test substance was administered (groups B and C). As shown in Table 1, the number of stimulations in which AD was not induced in the frontal cortex significantly increased depending on the concentration of theanine administered.
On the other hand, as shown in Table 3, administration of theanine had little effect on the induction of AD in the hippocampus on the opposite side of stimulation. Especially, compared to Group B (100 μmol / kg order), C
The effect of the group (mmol / kg order) was remarkable.

As shown above, it was revealed that administration of theanine suppresses the appearance or development of AD. Also, the process of creating epilepsy model animals
The appearance of AD ⇒ development of AD ⇒ Considering that it is completed through the process of convulsion, the administration of theanine to a patient in a state in which abnormal discharge of AD is likely to occur in the brain causes the appearance of AD-like abnormal discharge. Or its development is suppressed,
As a result, it can be considered that secondary epilepsy with convulsion, which is considered to be a sequelae, can be prevented. Examples of the state in which AD-like abnormal discharge is likely to occur in the brain include disorders during delivery and head injury.

[Experiment 2] In this experiment, the inhibitory action of theanine on the appearance of post-emission (“AD”) during the creation of an electric kindling model using experimental animals, in particular, the effect of intracerebroventricular administration of theanine was examined.

(Preparation of Specimen Animal) 10-week-old Wista
After preliminarily breeding r-type male rats in the following environment, those having a body weight of 280 g or more were selected, and an implantation operation of a chronic electrode and a cannula for intraventricular administration was performed in the following manner.

= Preliminary breeding environment = Breeding room: Small animal control room (rat breeding room) Temperature: 20 ± 3 ° C. Humidity: 50 ± 10% Light / dark cycle: Light up from 08:00 to 20:00 Working cage: Polycarbonate cage ( Cage exchange: 2 times / week Feeding: Solid feed (CE-1, CLEA Japan, Inc.) free water supply: Tap water filtered with Millipore filter is freely taken.

= Chronic electrode and cannula implantation surgery for intraventricular administration = Anesthesia: Bent barbital anesthesia implantation site: on left and right frontal dura, on left and right hippocampus dorsal side, third ventricle use electrode: epidural Electrode: Stainless steel screw electrode Deep electrode: Stainless steel parallel type bipolar electrode (for both recording and stimulation) Dosing cannula: Stainless steel pipe (φ
Postoperative treatment: Sulfa drug was encapsulated in the incision at the time of suturing, and 3000 units of penicillin G potassium solution was intramuscularly administered for 5 days after the surgery to prevent infection. Show.

(Definition of AD Threshold) After Electrode Implantation Surgery 1
Animals aged 0 days or more were moved into the measurement box, and a rectangular wave having a frequency of 60 Hz and a duration of 1 second was applied to the dorsal part of the right hippocampus at 24 hour intervals via an isolator. The energization amount is set to 100 μA for the first time, the energization amount is increased by 50 μA until AD is recognized, and the AD threshold value is determined. The subsequent stimulation is performed at this AD threshold value, and animals that induce AD for three consecutive days are tested. used. When AD was not expressed at the AD threshold initially set during the three days, stimulation was performed by increasing the energization amount by 50 μA from the next day, and this operation was repeated.

EEGs before and after stimulation (cortex, stimulus side or hippocampus on the opposite side) were derived by wire, recorded on paper after amplification, and stored on a magneto-optical disk at a sampling frequency of 200 Hz. The recording conditions are a time constant of 0.1 seconds, a high cutoff frequency of 60 Hz, an attenuation characteristic of 24 dB / octave, and a recording time of 1 minute before stimulation and 4 minutes after stimulation, which is a total of 5 minutes. In addition, an image obtained by a CCD camera attached to a measurement box for observing the reaction of the animal before and after stimulation was recorded simultaneously with the electroencephalogram using a digital video recorder.

= Equipment used = Stimulator: Electrical stimulator (SEN-7203, Nihon Kohden) Isolator: Isolator (SS-201J, Nihon Kohden) Amplifier: Bioelectric amplifier (AB621G, Nihon Kohden) Recorder: Thermal pen type recorder (8R-33, NEC Medical Systems) AD converter: AD conversion board (ADM-5298BPC, Microscience) Others: Personal computer, oscilloscope, magneto-optical disk drive, CCD camera, digital video tape recorder

(Administration experiment) 0.1 ml of a test substance (L-theanine (manufactured by Tokyo Kasei Co., Ltd.) dissolved in sterilized physiological saline was pre-fixed into the third ventricle (constant volume). ).

A dosing experiment was carried out for a total of 6 groups including a control group and a theanine administration group (5 groups), with 7 model animals as one group. After a washout period of 3 days or more, each individual was administered 3 times. Group A: 0 μmol / kg (saline administration group, control group) Group B: 20 μmol / kg Group C: 40 μmol / kg Group D: 60 μmol / kg Group E: 80 μmol / kg Group F: 100 μmol / kg

15 minutes after administration of the test substance, stimulation was performed with an energizing amount of the AD induction threshold. Electroencephalograms and behaviors 1 minute before and 2 minutes after stimulation were recorded under the same conditions as when the AD threshold was confirmed. After a washout period of 3 days, administration of the same concentration was performed 3 times.

The presence or absence of AD induction was confirmed from the recorded electroencephalogram, and the average amplitude of 10 discharges with large amplitude (average maximum amplitude)
And AD duration was measured. Kruskal-Wallis test was used for the average maximum amplitude and duration of AD, and chi-square test was used for the presence or absence of AD.

(Results) Table 5 shows changes in the average maximum amplitude of AD in the cortex and hippocampus, FIG. 8 shows the average maximum amplitude of AD in each group in the cortex, and FIG. 9 shows the average AD in each group in the hippocampus. Indicates the maximum amplitude. In addition, Table 6 shows whether or not there is a significant difference between AD groups in the AD average maximum amplitude in the cortex.
Indicates whether or not there is a significant difference between the groups in AD mean maximum amplitude in the hippocampus. Depending on the concentration of theanine administered,
The AD mean maximum amplitude decreased in both hippocampal regions. The large standard deviation of each group depends on the concentration of theanine administered.
This is because the number of individuals that do not induce D at all (AD amplitude is 0 μV) has increased.

[0045]

[Table 5]

[0046]

[Table 6]

[0047]

[Table 7]

Table 8 shows changes in AD duration in the cortex / hippocampus, FIG. 10 shows AD duration of each group in the cortex, and FIG. 11 shows AD duration of each group in the hippocampus. Further, Table 9 shows the presence / absence of a significant difference between the groups in AD duration in the cortex, and Table 10 shows the presence / absence of a significant difference in the AD duration in the hippocampus between the groups. Similar to amplitude, AD duration was shortened in both cortical and hippocampal regions depending on the concentration of theanine administered. The large standard deviation of each group is due to the increase in the number of individuals (AD duration 0 sec) that does not induce AD at all, similar to the amplitude.

[0049]

[Table 8]

[0050]

[Table 9]

[0051]

[Table 10]

Table 11 shows the presence or absence of AD induction, and Table 12 shows the significant difference in the presence or absence of AD induction between the groups. The number of individuals that did not induce AD in both cortex and hippocampus increased depending on the concentration of theanine administered. When AD was induced, it was induced in both cortical and hippocampal regions, and when it was not induced, it was not induced in both regions.

[0053]

[Table 11]

[0054]

[Table 12]

In this experiment by intraventricular administration, 40 μ
Administration of mol / kg completely suppressed the induction of AD in 3 of 7 animals, and administration of 100 μmol / kg completely suppressed the induction of AD in 6 of 7 animals. Moreover, both the amplitude and duration of the induced AD decreased depending on the concentration when theanine was administered at 40 μmol / kg or more. With intraventricular administration,
Many individuals did not induce AD completely, and the standard deviation became large. Therefore, there was no significant difference in AD amplitude and duration at 40 μmol / kg from the control group, but the actual effect was 2 mmol / kg. It is considered to be stronger than intravenous administration.

[Brief description of drawings]

FIG. 1 is an explanatory diagram showing a method of measuring an AD average maximum amplitude (a method of measuring the amplitudes of 10 discharges having a large amplitude from among induced AD and calculating an average value thereof) of an embodiment,
In this figure, the upper row (CORTEX) shows the frontal cortex and the lower row (HIPP) shows the contralateral hippocampus.

FIG. 2 is a method of measuring AD duration of an example (the time from AD that first appeared to last AD after stimulation was A
FIG. 6 is a diagram illustrating a method of setting D duration), in which the upper row (CORTEX) is the frontal lobe cortex and the lower row (HI).
(PP) indicates the hippocampus on the other side of stimulation.

FIG. 3 is a graph showing the effect of administration of the test substance of Example on the AD average amplitude in the frontal cortex.

FIG. 4 is a graph showing the effect of the administration of the test substance of Example on the AD mean amplitude in the hippocampus on the contralateral side of stimulation.

FIG. 5 is a graph showing the effect of administration of the test substance of Example on AD duration in the frontal cortex.

FIG. 6 is a graph showing the effect of administration of the test substance of Example on AD duration in the hippocampus on the contralateral side of stimulation.

FIG. 7 is a photograph showing the head of a sample animal one week after the implantation of a pipe for electrode / ventricular administration.

FIG. 8 is a graph showing the average maximum amplitude of AD in each group in the cortex.

FIG. 9 is a graph showing the average maximum amplitude of AD of each group in the hippocampus.

FIG. 10 is a graph showing AD duration of each group in the cortex.

FIG. 11 is a graph showing AD duration of each group in the hippocampus.

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Noriyoshi Okamura             3-33, Yotominami 3-chome, Matsuyama City, Ehime Prefecture F-term (reference) 4C206 AA01 AA02 GA18 GA22 MA01                       MA04 NA14 ZA06

Claims (2)

[Claims] 1. An antiepileptic agent and a therapeutic agent containing at least one or more of theanine and its derivatives as an active ingredient. 2. The above-mentioned theanine and its derivatives are L-glutamic acid-γ-ethylamide and L-glutamic acid-γ.
-L- or D-glutamic acid-γ-alkylamide such as methylamide, D-glutamic acid-γ-ethylamide and D-glutamic acid-γ-methylamide, and a derivative containing L- or D-glutamic acid-γ-alkylamide in the basic structure The antiepileptic agent and therapeutic agent according to claim 1, which is a mixture of one or two or more compounds selected from the group consisting of: