JP2008184448A - Psychotropic agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a psychotropic agent excellent in psychotropic action with little adverse effects. <P>SOLUTION: The psychotropic agent contains Kangen (a kind of traditional Chinese medicines) granules as an active ingredient and is used, e.g., as a tranquilizer, an antimanic agent, a sedative agent, a sleeping drug and the like. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a psychotropic agent, and more particularly to a psychotropic agent containing a crown granule as an active ingredient.

  Traditionally, there are four types of herbs: safflower, peony, senkyu, and tanjin, which have the effect of “revitalizing” as herbal ingredients, and scented kobushi and woody incense. There is known a crown granule prepared by blending two kinds of herbs (Mokkou) at a predetermined blending ratio. Conventionally, coronal granule has been applied to improve symptoms such as headache, stiff shoulders, dizziness, palpitation and the like of middle-aged persons or those with a tendency to hypertension by various active ingredients. Moreover, the effect | action which suppresses the aging of a cell and the complication of diabetes which are described in patent document 1, 2 is also known.

  By the way, modern people are subjected to physical stress such as noise, chemical stress such as exhaust gas, or psychosocial mental stress in daily life. For example, when an animal is stressed and the stress is accumulated, the mental state may change to an unhealthy state. For example, symptoms of epilepsy such as wheezing, hyperactivity, aggressive behavior, etc., or behavioral atrophy symptoms such as anxiety, weakness, etc., and further worsening may cause mental disorders such as manic depression and nervous breakdown There is.

  Conventionally, for example, vascular dementia that appears after cerebral ischemia due to a stroke such as cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage or the like is known. In vascular dementia, it is known that memory impairment and cognitive impairment occur as core symptoms, and mental symptoms such as activity disorder, aggression, and agitation occur as peripheral symptoms.

Conventionally, as a drug for treating these psychiatric disorders, a psychotropic agent that is a drug that acts on the central nerve and affects the mental function is known. Specific examples of the psychotropic agent include a tranquilizer, an antidepressant, a sedative, a sleeping agent, a hypnotic, an antidepressant, and an anxiolytic agent. For example, phenothiazine compounds such as ethylamino derivatives, butyphenone compounds such as haloperidol, lithium carbonate as an antidepressant, tricyclic compounds such as amitriptyline as an antidepressant, and the like are known as tranquilizers.
JP 2006-28155 A JP 2006-63076 A

  However, the above-mentioned phenothiamine compounds and butyphenone compounds, which are tranquilizers, and tricyclic compounds, which are antidepressants, have problems that cause side effects such as dry mouth and constipation due to the effect of anticholinergic action. In addition, lithium carbonate, an antidepressant, has been reported to have side effects such as digestive / circulatory disorders, urinary abnormalities, and endocrine abnormalities.

  As a result of diligent research by the present inventors, the present inventors have elucidated a novel pharmacological action that a crown granule made of a natural herb component has a psychotropic action such as a tranquilizing action, an antidepressant action, a sedative action and a sleep action. It was made by doing. The aim is to provide a psychotropic agent with few side effects and excellent psychotropic effects.

In order to achieve the above object, the psychotropic agent of the invention described in claim 1 is characterized in that it contains a crown granule as an active ingredient.
The invention described in claim 2 is characterized in that, in the psychotropic agent described in claim 1, it is used as at least one selected from a tranquilizer, an antidepressant, a sedative, and a sleep agent.

  ADVANTAGE OF THE INVENTION According to this invention, there can be provided a psychotropic agent with few side effects and excellent psychotropic action.

Hereinafter, an embodiment of a psychotropic agent embodying the present invention will be described.
The psychotropic agent of this embodiment contains a crown granule as an active ingredient. A psychotropic agent refers to a drug that affects the mental function by acting on the central nervous system. More specifically, for example, a drug exhibiting a psychiatric / neurological action such as a tranquilizing action, an antidepressant action, a sedative action, a sleeping action, a hypnotic action, a central nerve stimulating action, an antidepressant action and an anxiolytic action is shown. The psychotropic agent of this embodiment exhibits these psychiatric / neurological effects by the crown granule blended as an active ingredient. That is, the psychotropic agent of the present embodiment includes a tranquilizer (major tranquilizer), an antidepressant, a sedative, a hypnotic, a hypnotic, a central nervous stimulant for the purpose of exerting these mental / nerve effects, As a minor tranquilizer, it can be suitably used as an antidepressant, an anxiolytic and the like. The psychotropic agent of the present embodiment is particularly preferably used as a tranquilizer, an antidepressant, a sedative, and a sleeping agent because it is particularly excellent in tranquilizing action, antidepressant action, sedative action, and sleeping action. .

  By the way, modern people are subjected to various stresses such as physical stress such as noise, chemical stress such as exhaust gas, or psychosocial mental stress in daily life. For example, when an animal is stressed and the stress is accumulated, the mental state may change to an unhealthy state. For example, epilepsy symptoms such as wheezing, hyperactivity, and aggressive behavior, or depressive symptoms such as anxiety, weakness, and behavior atrophy. As these symptoms worsen, mental disorders such as manic depression and nervous breakdown occur. Depressive illness is a mental condition in which the mood rises and it is difficult to control one's behavior and thoughts, and the psychological symptoms that are depressed in the mood and the depression in which the amount of action decreases due to anxiety or lethargy. Say.

  The psychotropic agent of this embodiment has psychotropic effects such as tranquilizing action, antidepressant action, sedative action, sleep action, hypnotic action, central nerve stimulating action, antidepressant action and anxiolytic action, and so on. It can be suitably used for patients with psychiatric disorders arising from The coronal granule, which is an active ingredient, is excellent in tranquilizing action, antidepressant action, sedative action and sleep action, and is therefore preferably applied to patients with epilepsy symptoms and patients with manic-depressive symptoms.

  Conventionally, for example, vascular dementia that appears after cerebral ischemia due to a stroke such as cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage or the like is known. In vascular dementia, it is known that memory impairment and cognitive impairment occur as core symptoms, and mental symptoms such as activity disorder, aggression, and irritability occur as peripheral symptoms. The psychotropic agent of this embodiment is also effective in improving peripheral symptoms of these vascular dementias. The psychotropic agent of this embodiment is preferably applied also to patients with vascular dementia.

  As a method for evaluating psychotropic agents, for example, a model in which normal animals such as mice and rats are stressed (exogenous model), and a drug administration and brain destruction model (endogenous model) are used. As an exogenous model, for example, there is a method in which the subject individual is subjected to stress such as separation breeding stress, electric shock that cannot be escaped, forced running, forced swimming, restraint stress, etc., and causing drought, anxiety, depressive symptoms, etc. Can be mentioned. Examples of the endogenous model include a method of inducing a manic state by administering a drug having a central nervous stimulating action such as methamphetamine to a target individual. Moreover, the method of causing anxiety and depression by administering drugs, such as reserpine, 5-hydroxytryptamine (serotonin), (beta) -carboline, is mentioned. In addition, the combined use with a substance having a sedative action such as thiopental can evaluate the effect of the psychotropic agent by observing the enhancement or decrease of the sedative action.

  The crown granule, which is the active ingredient of this embodiment, has four types of herbs, safflower, peony, tankyu, and tanjin, which have the effect of “revitalize” as herbal ingredients, It is a Chinese herbal medicine (Chinese herbal medicine) prepared by blending two kinds of herbs, Kobushi (Kubushi) and Mika (Mokko), which have an action (improves feelings).

  This coronal granule was born in China in the 1960s from research on therapeutic agents for cerebrovascular and cardiovascular diseases. In 1969, Kannashin Ichigo consisted of 9 kinds of herbal medicines, followed by 5 kinds in 1978. Kannashin No. 2 consisting of herbal medicines (tansan, glaze, senkyu, safflower, and incense) was born, and the crown granule, in which incense was replaced with incense and incense, was approved as a pharmaceutical product in Japan in 1990. .

  The compounding ratio of each constituent crude drug contained in the crown granule is 2.6 to 6.8 parts by weight of Dansan, 0.6 to 1.7 parts by weight of Katsuki, 0.6 to 1.7 parts by weight of incense, and safflower. 1.1 to 3.4 parts by weight, 1.1 to 3.4 parts by weight of glaze, and 1.1 to 3.4 parts by weight of senkyu are preferable, and the weight ratio of Dansang, Katsuki, Mika, safflower, glaze and senkyu 4: 1: 1: 2: 2: 2 is more preferable. This coronal granule has been known to have the efficacy and effect of improving various symptoms such as headache, head weight, stiff shoulders, dizziness, palpitation, etc., although it has been in the middle age or higher than before.

  Dansang is the root of the Labiatae perennial tanjin (Salvia miltiorrhiza Bunge). Katsuki is the rhizome of the perennial grasshopper (Cyperus rotundus Linne) in the family Cyperaceae. Incense is the root of the perennial South Leapala (Auslandia lappa Decne (Saussurea lappa Clarke)) of the Compositae family. The safflower is a tubular flower of the plant safflower (Carthamus tinctorius Linne) of the Compositae 1-2 year. The glaze is the root of the perennial peony (Paeonia lactiflora Pallas) in the Paeoniaceae family. The nematode is the rhizome of the perennial nematode (C nidium officinale Makino) of the Umbelliferae family.

  The crown granule is obtained by mixing the constituent crude drugs at a predetermined blending ratio and extracting the mixture with hot water using 5 to 30 times, preferably 10 to 20 times the amount of the total weight of the mixture. A granular product produced by concentrating and drying an aqueous extract (crown granule extract). The concentration and drying are performed by conventional means such as a vacuum evaporation concentration method, a spray drying method, a freeze drying method and the like. According to the production method of this crown granule, for example, Dansan 4.5 g, Katsuki 1.125 g, Kikko 1.125 g, Safflower 2.25 g, Glaze 2.25 g and Senkyu 2.25 g (total 13.5 g) From this, a crown granule having a solid content of 4.5 g is obtained. The crown granule produced in this way is used as a psychotropic agent in this embodiment.

  The crown granule (solid matter) thus obtained may be taken as it is in the form of a powder or powder, or it may be used together with suitable excipients, bases, emulsifiers, solvents, stabilizers and other additives. , Tablets, capsules, pills, suppositories, solutions, injections, etc. may be processed and administered. Moreover, it is also possible to process and take in the form of a drink etc. based on the hot water extract before the said drying or its concentrate.

  The psychotropic agent is formulated so that the crown granule as an active ingredient is preferably administered in an amount of about 1 to 20 g, more preferably about 4.5 g per day for an adult, and the daily dose is administered several times a day (three times). It is particularly preferable to be prescribed to be taken between meals or on an empty stomach. The psychotropic agent containing the crown granule as an active ingredient can be used for pharmaceutical or food use by containing it in a medicine such as Chinese medicine or a food such as health food or general food.

According to the psychotropic agent of the present embodiment, the following effects can be obtained.
(1) In the psychotropic agent of this embodiment, the crown granule with which 6 types of crude drug components are mix | blended contains as an active ingredient. Therefore, psychotropic action can be exhibited by ingestion.

  (2) The psychotropic agent of the present embodiment can particularly effectively exert a tranquilizing action, an antidepressant action, a sedative action and a sleep action by the crown granule which is an active ingredient. Therefore, it is expected that it can be suitably used for the treatment of mental disorders such as manic symptoms.

(3) Since the psychotropic agent of the present embodiment is based on a herbal medicine that is already widely used as a raw material, there is no worry about side effects.
(4) Since the coronal granule, which is an active ingredient of the psychotropic agent of the present embodiment, is also used as an agent for improving learning / memory impairment due to cerebral ischemia, by applying it to a patient with vascular dementia, It is expected not only to improve symptoms (memory impairment and cognitive impairment), but also to improve peripheral symptoms (psychiatric symptoms such as activity disorder, aggression, and agitation).

  (5) In addition, the coronal granule blended as an active ingredient in the psychotropic agent of the present embodiment has other medicinal properties (effects / effects for improving various symptoms such as headache, head weight, stiff shoulders, dizziness, palpitation, Since they have an action to suppress complications), their effects can be expected by ingestion.

In addition, the psychotropic agent of this embodiment can also be changed and embodied as follows.
-The psychotropic agent of this embodiment is applied, for example to the treatment of the patient who has a psychiatric disorder. However, not only for therapeutic use, but also for healthy people to take for the prevention of mental illness.

-Since the psychotropic agent of this embodiment has the effect | action which reduces mental symptoms, such as a manic symptom resulting from stress, you may use it as a stress reducing agent.
-The psychotropic agent of this embodiment is not only administered for the purpose of treatment or prevention of mental illness resulting from stress or peripheral symptoms of vascular dementia, but may also be applied to patients with other psychiatric disorders Good.

  -The psychotropic agent of this embodiment is administered to domestic animals (non-human mammals) such as horses, cows and pigs, poultry such as chickens, or pets such as dogs, cats, rats and mice in addition to humans. May be.

  The crown granule, which is the active ingredient, may be contained in taste products such as bread, cakes and snacks, dairy products such as milk and yogurt, and beverages such as soft drinks.

Next, the embodiment will be described in more detail with reference to each test example.
(Preparation of crown granules)
The constituent crude drug of the crown granule used in this test and its content are: 2.25 g glaze, 2.25 g nematode, 2.25 g safflower, 1.125 g cabbage, 1.125 g wood incense and 4 It consists of .5g of Dansang. 20 times the amount of water was added to the mixture of these constituent crude drugs, and hot water extraction was performed at 100 ° C. for 1 hour. Then, after filtration, the filtrate was concentrated under reduced pressure to distill off the solvent, whereby a 44% yield of crown granule (crown granule extract) was obtained.

Test Example 1 (Effects of crown granules on methamphetamine-treated mice)
Methamphetamine is a compound having a structure in which a methyl group is substituted for amphetamine. Methamphetamine is a compound having central nervous excitability. Using 5-week-old male ddY mice, the effect on the central nerve of the coronal granule was examined by measuring the change in momentum when methamphetamine was administered to the mouse to which the coronal granule was administered.

  First, mice were grouped into 4 groups (control group and groups 1 to 3), 10-11 mice per group. Next, for the mice of the first group, the second group, and the third group, 60 minutes of the exercise amount measurement so that the crown granule is dosed at 30 mg / kg body weight, 100 mg / kg body weight, and 300 mg / kg body weight, respectively. Prior to oral administration to mice. Mice to which only an excipient (dextrin) that does not contain the crown compound as an active ingredient was given as a control (Vehicle).

  Next, methamphetamine 1 mg / kg body weight was intraperitoneally administered 30 minutes before the momentum measurement, and changes in the momentum (Ambulation) were measured 1 hour, 2 hours and 3 hours after the administration of the crown granule. The amount of exercise was measured using an open-field device divided into 19 sections, and the number of times of traversing each section in 3 minutes was measured, and the total number was shown as the amount of exercise. The results are shown in FIG.

  As shown in FIG. 1, in the control (Vehicle) mouse, it is confirmed that the momentum increases remarkably 1 hour after methamphetamine administration, and thereafter the exercise amount gradually returns to before the administration. It is confirmed that in the mice administered with 30 mg / kg body weight of the crown granule and 100 mg / kg body weight, the amount of exercise after 1 hour is significantly suppressed as compared with the control mice. Further, it was confirmed that the mouse administered with 300 mg / kg body weight of the crown granule further suppressed the increase in momentum after 1 hour than the mice administered with 30 mg / kg body weight of the crown granule and 100 mg / kg body weight. From the above, it was confirmed that the crown granule has an action of suppressing an increase in momentum due to methamphetamine.

Test Example 2 (Effect of crown granule on aggressive behavior after single isolation rearing)
Using 7-week-old Wistar rats, they were isolated and bred for 2 weeks or longer, and the attack behaviors developed after the administration of the crown granules were examined to examine the influence of the crown granules on the attack behavior. Mental stress can be applied to the rat by keeping the rat isolated. Rats that have undergone mental stress and accumulate stress acquire a higher aggression than before stress loading. Conventionally, it has been used as an exogenous stress load model.

  First, rats were grouped into 3 groups (control group, group 1 and group 2), 10 rats per group. Then, an exogenous stress-bearing rat was prepared by individually rearing the rats of the control group, the first group and the second group. Subsequently, the explants of exogenous stress in the first group and the second group were orally administered with the coronal granule so as to have a dosage of 30 mg / kg body weight and 100 mg / kg body weight, respectively. Rats to which only an excipient (dextrin) containing no coronal granules as an active ingredient was given as a control (Vehicle).

  The attack response (Attack Response) with respect to the stick extended to the tip of the nose was evaluated before and after coronal granule administration (30 minutes, 1 hour, 2 hours, 4 hours) with a four-level score (Score). In each rat group, rats showing a score of 4 before the administration of coronal granules were selected. No attack response was scored 0. The challenge response of half of the rats showing a score of 4 before administration of the coronal granule was score 2, and between score 4 and score 0 was score 3 and score 1, respectively. The results are shown in FIG.

  As shown in FIG. 2, the control (Vehicle) rats decreased to score 3 1 hour after administration, and thereafter a slight increase in score was confirmed over time. Rats with 30 mg / kg body weight of crown granule showed no significant difference compared to control rats. The rat administered with 100 mg / kg body weight of the crown granule decreased to a score of around 30 minutes after administration, and showed a score of around 1.5 until 1 hour and 2 hours after administration. Based on the above, it was confirmed that the crown granule has an action of suppressing the aggressive behavior that increases after individual isolation breeding.

Test Example 3 (Effect of crown granule on sleep action by thiopental sodium)
Thiopental sodium is one of barbital anesthetics and has sedative and sleep effects. Using 4-week-old ddY male mice, changes in sleep time when thiopental sodium was administered to mice administered with coronal granules were examined to determine the effect of the coronal granules on the sleep action.

  First, mice were grouped into 4 groups (control group and groups 1 to 3), 6-9 mice per group. Then, to the mice of the first group, the second group, and the third group, the coronal granule was orally administered to the mice so that the doses of 30 mg / kg body weight, 100 mg / kg body weight, and 300 mg / kg body weight were respectively obtained. . Mice to which only an excipient (dextrin) that does not contain the crown compound as an active ingredient was given as a control (Vehicle).

  To sleep by thiopental sodium, 60 mg / kg body weight of thiopental sodium was intraperitoneally administered to all mice one hour after the oral administration of the crown granule and the control group to mice. After the administration of thiopental sodium, the time from the disappearance of the direct reflex to the recovery was measured as the sleep time using the righting reflex (RR) as an index.

  As shown in FIG. 3, the control (Vehicle) mouse had a sleep time of about 5 hours. All the mice administered with 30 mg / kg body weight, 100 mg / kg body weight, and 300 mg / kg body weight of the granule have a sleep time of 10 hours or more, and the sleep time is significantly increased compared to the control mouse group. Was confirmed. From the above, it was confirmed that the crown granule has an action of prolonging the sleep action by thiopental sodium. As shown in the above experiments, it has been clarified that the crown granule has psychotropic effects such as a tranquilizing action, an antidepressant action, a sedative action, and a sleep action.

Next, technical ideas that can be grasped from the above-described embodiment and other examples will be described below together with their effects.
(A) A method for administering a psychotropic agent, wherein the active ingredient is administered in an amount of 30 to 300 mg / kg body weight / day. Therefore, according to the invention described in (a), the psychotropic effect can be effectively exhibited.

(B) A pharmaceutical or food or drink containing the psychotropic agent as an active ingredient. Therefore, according to the invention described in (b), the psychotropic agent can be efficiently taken.
(C) The psychotropic agent used as a stress reducing agent.

Effect of crown granules on the momentum increasing effect of methamphetamine. Effect of crown granule on aggressive behavior after isolation. Effect of crown granule on sleep action by sodium thiopental.

Claims (2)

  A psychotropic agent comprising crown granules as an active ingredient.   The psychotropic agent according to claim 1, which is used as at least one selected from a tranquilizer, an antidepressant, a sedative, and a sleeping agent.

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