WO2018034430A1 - Composition for preventing or treating mental disorder, containing lactobacillus plantarum-derived vesicle - Google Patents

Abstract

The present invention relates to a composition for preventing, improving or treating a mental disorder, the composition containing a Lactobacillus plantarum-derived vesicle as an active ingredient. The present inventors have confirmed that, when a Lactobacillus plantarum-derived vesicle is administered to a stress and depression animal model, resistance to stress efficiently increases, and an effect of treating chronically persisting long-term depression behavior is exhibited, and thus the Lactobacillus plantarum-derived vesicle, according to the present invention, may be usefully employed in developing a medicine or a functional health food, etc., for preventing, reducing the symptoms of or treating a mental disorder such as stress, anxiety disorder, post-traumatic stress disorder, panic disorder, depression, autism spectrum disorder, attention deficit hyperactivity disorder and schizophrenia.

Description

Composition for the prevention or treatment of mental diseases, including Lactobacillus plantarum-derived vesicles

The present invention relates to a composition for preventing, ameliorating, or treating mental disorders comprising Lactobacillus plantarum-derived vesicles as an active ingredient.

Depression is a condition in which negative emotions occur due to changes in the brain's ability to control emotions, and more than 300 million people around the world suffer from it. In addition, as a result of analyzing data on depression for five years from 2005 to 2009 according to the Korea Health Insurance Review and Assessment Service, the number of depressed patients and total medical expenses increased by 4% and 10.4% per year, respectively. Increased from 435,000 in 2005 to 500,300 in 2009, an increase of about 18,000 patients per year. In particular, the increase rate of the elderly over 70 is the highest.

Various studies have been attempted to determine the cause of depression, but the exact mechanism of neurological pathogenesis is not yet known, but there are a variety of causes. Depression is associated with chemical imbalances of neurotransmitters such as dopamine, serotonin and norepinephrine. Serotonin is a neurometabolic compound found in cerebrospinal fluid, which circulates in the brain and functions as a neurotransmitter. Serotonin is closely related to the expression of emotions, and the lack of this material leads to unstable emotions, increasing anxiety and worry, and impulsive tendencies. Therefore, there are many drugs currently used as antidepressants to prevent the re-absorption of serotonin to stay in the brain for a long time.

The etiology of depression includes biological, psychological, sociological, pharmacological, and pathological factors that affect neurotransmitter imbalances, especially mental trauma from childhood accidents, assaults, and abuse. It is known that the probability of development is very high. This is because stress causes protein damage in the human brain. The stressful environment, ie the boom of selfishness, rapid industrialization, intense competition and a lack of social safety nets for the underprivileged are known to cause environmental factors.

Antidepressants used in the treatment of depression include tricyclic antidepressants such as imipramine, and selective serotonin reuptake inhibitors (SSRI). However, SSRIs, such as Trazodone and Mirtazapine, have raised safety concerns, especially in older people, which may increase the risk of stroke, fracture, and death. .

Recently, mental illnesses such as depression, autism, and schizophrenia have been found to be deeply linked to stomach aches. Belly is accompanied by diarrhea and constipation, and repeated it leads to irritable bowel syndrome, which has been shown to be associated with gut microbial dysbiosis. If intestinal bacteria are imbalanced due to poor food or antibiotics, the intestinal harmful microorganisms cause cracks in the colonic protective shield, which leads to intestinal leakage, and the harmful bacteria-derived toxins are systemically absorbed, causing depression or worsening. (Pharmacotherapy. 2015 Oct; 35 (10): 910-6).

Lactobacillus plantarum is a Gram-positive bacillus that grows well in anaerobic as well as aerobic environments and is found in fermented foods such as kimchi. In the case of kimchi, other lactic acid bacteria die even if it becomes sour kimchi, but the bacteria are known to survive with excellent viability. The bacteria die, but the bacteria survive well and break down polysaccharides such as galactose and arabinose. Bacteria secrete extracellular vesicles (EVs), commonly referred to as nanovesicles or nanovesicles, as bilayer protein lipids into the extracellular environment for the exchange of information between proteins, lipids, genes, and the like. Gram-positive bacteria-derived vesicles, such as Lactobacillus plantarum, also contain peptidoglycan and lipoteichoic acid, which are bacterial cell wall components.

It is known that Lactobacillus plantarum secretes depressive factors in the brain, but vesicles secreted by Lactobacillus plantarum are stress and anxiety disorders. Post-traumatic Stress Disorder (PTSD), panic disorder, depression, Autism spectrum disorders, attention deficit / hyperactivity disorder (ADHD), and It has not been used for the prevention or treatment of mental illnesses such as schizophrenia.

The present inventors have studied intensively to find a correlation between Lactobacillus plantarum-derived vesicles and mental disorders. As a result, the administration of Lactobacillus plantarum-derived vesicles in stress and depression animal models is almost the same level as imipramine. It was observed that the anti-stress and anti-depressant effect, the present invention was completed based on this.

Accordingly, an object of the present invention is to provide a composition for the prevention, improvement or treatment of mental disorders, including the Lactobacillus plantarum-derived vesicles as an active ingredient.

However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problem, another task that is not mentioned will be clearly understood by those skilled in the art from the following description.

In order to achieve the object of the present invention as described above, the present invention provides a pharmaceutical composition for the prevention or treatment of mental disorders, including Lactobacillus plantarum- derived vesicles as an active ingredient.

In another aspect, the present invention provides a functional food composition for improvement of mental disorders, including Lactobacillus plantarum-derived vesicles as an active ingredient.

The present invention also provides an inhalation composition for the prevention or treatment of mental disorders, comprising Lactobacillus plantarum-derived vesicles as an active ingredient.

In another embodiment of the present invention, the mental illness is stress, anxiety disorder. Post-traumatic Stress Disorder (PTSD), panic disorder, depression, Autism spectrum disorders, attention deficit / hyperactivity disorder (ADHD), and May be one or more diseases selected from the group consisting of schizophrenia.

In another embodiment of the present invention, the vesicles may have an average diameter of 10 to 1000 nm.

In another embodiment of the present invention, the vesicles may be separated from the Lactobacillus plantarum culture.

In another embodiment of the present invention, the vesicles may be secreted naturally or artificially in Lactobacillus plantarum.

In another embodiment of the present invention, the vesicle may be a vesicle separated from the food prepared by adding the Lactobacillus plantarum.

In another embodiment of the present invention, the vesicles may be derived from Lactobacillus genus bacteria other than Lactobacillus plantarum.

The present invention also provides a method of preventing or treating mental disorders, comprising administering the composition to a subject.

The present invention also provides a preventive or therapeutic use of Lactobacillus plantarum-derived vesicles.

The inventors have found that when Lactobacillus plantarum-derived vesicles are administered to stress and depression animal models, the resistance to stress is effectively increased, and there is an effect of treating chronic long-term depressive behavior. According to Lactobacillus plantarum derived vesicles are stress, anxiety disorders. Useful in the development of medicines or dietary supplements to prevent, ameliorate, or treat mental disorders such as post-traumatic stress disorder, panic disorder, depression, autism spectra disorder, attention deficit hyperactivity syndrome, and schizophrenia Can be.

FIG. 1 graphically illustrates an experimental protocol for evaluating the antistress effect of Lactobacillus plantarum-derived vesicles (EV) in a stressed mouse model [CON or CON + Veh: Saline-administered normal mice (control) , Saline administration control group), CON + EV: vesicle administration normal mouse group, RST + Veh: saline administration stress treatment group, RST + EV: vesicle administration stress treatment group].

Figure 2 is a method for evaluating the anti-stress effect of the Lactobacillus plantarum-derived vesicles, a graphical illustration of the U-Box test test method for measuring the sociality for each mouse group.

Figure 3 shows the results of the U-Box test for each group of mice to evaluate the anti-stress effect of the Lactobacillus plantarum-derived vesicles.

FIG. 4 shows a tail suspension test (TST) and a forced swim test (FST) for each group of mice to evaluate the anti-stress effect of Lactobacillus plantarum-derived vesicles. The results are shown.

FIG. 5 graphically depicts an experimental protocol for evaluating the antidepressant effect of Lactobacillus plantarum-derived vesicles (EV) in a mouse model induced by depression as a result of chronic stress [CON + Veh: normal saline administration] Mouse group, CON + EV: vesicle-administered normal mouse group, RST + Veh: saline-administered chronic stress treatment group, RST + EV: vesicle-administrated chronic stress treatment group, RST + IMI: imipramine-treated chronic stress treatment group].

Figure 6 shows the results of the U-Box test for each group of mice as a primary behavioral test to evaluate the antidepressant effect of Lactobacillus plantarum-derived vesicles.

FIG. 7 shows the results of conducting a tail suspension test (TST) and a forced swimming test (FST) for each group of mice as a primary behavioral test for evaluating antidepressant effects of Lactobacillus plantarum-derived vesicles.

Figure 8 shows the results of the U-Box test for each group of mice as a second behavioral test to evaluate the antidepressant effect of the Lactobacillus plantarum-derived vesicles.

FIG. 9 shows the results of conducting a tail suspension test (TST) and a forced swimming test (FST) for each group of mice as a second behavioral test for evaluating antidepressant effects of Lactobacillus plantarum-derived vesicles.

The present inventors have studied intensively to find a correlation between Lactobacillus plantarum-derived vesicles and mental disorders. It was observed that the anti-stress and anti-depressant effect, the present invention was completed based on this.

In one embodiment of the present invention, after administering the Lactobacillus plantarum-derived vesicles to the mouse model subjected to body detention stress, each of three types of behavioral tests, namely, the U-BOX test, tailing test and forced test The anti-stress effect was confirmed in the mice administered with the nanovesicles compared to the stress-treated mice by the swimming test (see Example 1).

In another embodiment of the present invention, after administering the Lactobacillus plantarum-derived vesicles to a mouse model inducing chronic stress-induced depressive behavior, the vesicles were analyzed by performing the same three kinds of behavioral tests. It was confirmed that the effect was shown (see Example 2).

Accordingly, the present invention provides a pharmaceutical composition for the prevention or treatment of mental disorders comprising Lactobacillus plantarum-derived vesicles as an active ingredient.

As used herein, the term "psychiatric disease" refers to a morbid mental state that affects a person's thinking, emotions, and behaviors, and refers to a state in which a disorder in mental function has been brought. In the present invention, the mental illness is stress, anxiety disorder. Post-traumatic Stress Disorder (PTSD), panic disorder, depression, Autism spectrum disorders, attention deficit / hyperactivity disorder (ADHD), and Schizophrenia and the like.

The term stress, as used herein, is a nonspecific biological response that occurs in the body to various injuries and stimuli to the living body, first named by Canadian endocrinologist H. celier. The stress response is a stimulating hormone, adrenaline or other hormone, that is secreted into the blood to protect our bodies, providing the strength and energy to fight the danger or avoid the situation. Common symptoms of stress vary, but physical symptoms such as fatigue, headache, insomnia, stomach disease, abdominal pain, vomiting, mental symptoms such as decreased concentration or memory, indecisiveness, emptiness, anxiety, nervousness, depression, anger, Emotional symptoms, such as frustration, and behavioral symptoms such as restlessness, nervous habits, and smoking.

As used herein, the term "depressive disorder" refers to a disease that causes various cognitive and psychosomatic symptoms due to decreased motivation and depression as main symptoms, leading to a decrease in daily functioning. Depression is known to be caused by environmental factors such as biochemical factors, genetic factors, and strong stress due to neurotransmitter or hormone imbalance. It is known to be prevented by the help of stress control, friendships and social support during times of crisis.

As used herein, the term prophylaxis means any action that inhibits mental retardation or delays onset by administration of a pharmaceutical composition according to the present invention.

As used herein, the term "treatment" refers to any action in which symptoms caused by mental disorders are improved or advantageously changed by administration of the pharmaceutical composition according to the present invention.

The vesicles of the present invention can be isolated from the culture of Lactobacillus plantarum or food prepared by adding Lactobacillus plantarum, and may be naturally or artificially secreted from Lactobacillus plantarum, but is not limited thereto. It doesn't happen.

The method for separating the vesicles from the culture solution or fermented food of the Lactobacillus plantarum of the present invention is not particularly limited as long as the vesicles. For example, centrifugation, ultra-fast centrifugation, filtration by filter, gel filtration chromatography, pre-flow electrophoresis, or capillary electrophoresis, and combinations thereof may be used to separate the vesicles and also remove impurities. It may further include a process for washing, concentration of the obtained vesicles and the like.

The vesicles separated by the method in the present invention may have an average diameter of 10 to 1000 nm, but is not limited thereto.

The pharmaceutical composition according to the present invention includes Lactobacillus plantarum-derived vesicles as an active ingredient, and may include a pharmaceutically acceptable carrier. Such pharmaceutically acceptable carriers are conventionally used in the preparation, and include, but are not limited to, saline solution, sterile water, Ringer's solution, buffered saline, cyclodextrin, dextrose solution, maltodextrin solution, glycerol, ethanol, liposomes, and the like. If necessary, other conventional additives such as antioxidants and buffers may be further included. In addition, diluents, dispersants, surfactants, binders, lubricants and the like may be additionally added to formulate injectable formulations, pills, capsules, granules, or tablets such as aqueous solutions, suspensions, emulsions and the like. Suitable pharmaceutically acceptable carriers and formulations can be preferably formulated according to the individual components using methods disclosed in Remington's literature. The pharmaceutical composition of the present invention is not particularly limited in formulation, but may be formulated as an injection, inhalant, external preparation for skin, oral ingestion, and the like.

The pharmaceutical composition of the present invention can be administered orally or parenterally (eg, applied intravenously, subcutaneously, skin, nasal, airways) according to the desired method, and the dosage is determined by the condition and weight of the patient, disease Depending on the degree, drug form, route of administration, and time, it may be appropriately selected by those skilled in the art.

The composition according to the invention is administered in a pharmaceutically effective amount. In the present invention, the pharmaceutically effective amount means an amount sufficient to treat the disease at a reasonable benefit / risk ratio applicable to the medical treatment, and the effective dose level refers to the type, severity, drug activity, and drug of the patient. Sensitivity, time of administration, route of administration and rate of release, duration of treatment, factors including concurrent use of drugs, and other factors well known in the medical arts. The composition according to the present invention may be administered as a separate therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be single or multiple doses. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect in a minimum amount without side effects, which can be easily determined by those skilled in the art.

Specifically, the effective amount of the composition according to the present invention may vary depending on the age, sex, and weight of the patient, and generally 0.001 to 150 mg, preferably 0.01 to 100 mg per kg of body weight is administered daily or every other day or 1 It can be administered in 1 to 3 times a day. However, the dosage may be increased or decreased depending on the route of administration, the severity of obesity, sex, weight, age, etc., and the above dosage does not limit the scope of the present invention in any way.

In another aspect, the present invention provides a health functional food composition for improving mental disorders comprising Lactobacillus plantarum-derived vesicles as an active ingredient.

As used herein, the term improvement means any action that at least reduces the parameters associated with the condition being treated, for example the extent of symptoms.

In the health functional food composition of the present invention, the active ingredient may be added to the food as it is, or used with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient can be suitably determined according to the purpose of use (improving). In general, in the manufacture of food or beverages the compositions of the invention are added in an amount of up to 15% by weight, preferably up to 10% by weight relative to the raw materials. However, in the case of prolonged intake for health and hygiene purposes or health control purposes, the amount may be below the above range.

The health functional food composition of the present invention, in addition to containing the active ingredient as an essential ingredient in the indicated ratios, is not particularly limited to other ingredients, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. have. 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 conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of the natural carbohydrate can be appropriately determined by the choice of those skilled in the art.

In addition to the above, the nutraceutical composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), synthetic flavors such as synthetic and natural flavors, coloring and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof, Alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks and the like. These components can be used independently or in combination. The proportion of such additives may also be appropriately selected by those skilled in the art.

The present invention also provides an inhalant composition for the prevention or treatment of mental disorders, including Lactobacillus plantarum-derived vesicles as an active ingredient.

In the inhalant composition of the present invention, the active ingredient may be added to the inhalant as it is, or may be used together with other ingredients, and may be appropriately used according to conventional methods. The amount of the active ingredient to be mixed may be suitably determined depending on the purpose of use (prophylactic or therapeutic).

In another aspect of the present invention, the present invention provides a method for preventing or treating mental disorders comprising administering to a subject a composition comprising a Lactobacillus plantarum-derived vesicle as an active ingredient.

In the present invention, an individual means a subject in need of treatment of a disease, and more specifically, a mammal such as a primate, mouse, rat, dog, cat, horse, and cow, which is human or non-human. Means.

Hereinafter, preferred examples are provided to aid in understanding the present invention. However, the following examples are merely provided to more easily understand the present invention, and the contents of the present invention are not limited by the following examples.

EXAMPLE

Example 1. Anti-stress effect confirmed by Lactobacillus plantarum-derived vesicles

Through experiments using mice, we tried to find out if the combination of Lactobacillus plantarum-derived nanovesicles prevents the depressive behavior induced by stress. For this purpose, according to the experimental procedure shown in Figure 1, 7-week-old male C57BL / 6 mice purchased four groups, that is, a normal group of mice administered saline (0.9% Saline, 100 μl) for 14 days (CON or CON) + Veh), normal mice group (CON + EV) administered nanovesicles (2 ug / mouse / 100 μl), saline (0.9% Saline, Group (RST + Veh) administered 100 μl) and nanovesicles (EV, 2 ug / mouse / 100 μl) to mice subjected to body detention stress for 14 days for 2 hours daily (RST + EV) After conducting the experiment, U-BOX test, tail suspension test (TST), and forced swim test (FST), which measure sociability, were performed in order. The antistress effect was evaluated.

First, the U-BOX test was performed on four groups of mice that performed the above experiments. As shown in the figure of Figure 2, the test is to put the target mouse in the wire mesh on one side of the U-shaped field, only the wire mesh without the target mouse on the other side, the experimental method for checking how much time to contact the target mouse to be. As a result, as shown in FIG. 3, both field stayed with similar probability during the field adaptation period (Habituation, non-target condition, 5 minutes), but the results were different for each group under the target condition performed for 10 minutes, which is the actual behavior test. That is, in the control group (CON + Veh) and the control group (CON + EV), the time spent in the target space was increased compared to the time spent in the non-target space. In the group under stress of detention (RST + Veh), they stayed less in the target space, whereas in the group with nanovesicles (EV) (RST + EV), the time spent in the target space was similar to the control group. It was confirmed that this is increased.

Next, as a result of conducting a tail test and a forced swimming test, immortality was increased in the group subjected to body detention stress (RST + Veh) compared to the control group (CON + Veh), while nano-vesicles were administered together. In one group (RST + EV) it was confirmed that the immobility is reduced.

The results showed that the antistress effect was excellent when Lactobacillus plantarum-derived vesicles were administered in a stressed mouse model.

Example 2. Confirmation of antidepressant effect caused by Lactobacillus plantarum-derived vesicles

In addition to the results of Example 1, it was evaluated whether the depressive behavior induced as a result of chronic stress when Lactobacillus plantarum-derived nano-vesicles can be recovered. For this purpose, as shown in the figure of Figure 5, 7-week-old male C57BL / 6 mice purchased a random group of five mice, that is, a normal mouse group (CON + Veh) administered saline (0.9% Saline, 100 μl) for 14 days (CON + Veh) ), Normal mice group (CON + EV) to which nanovesicles (EV, 2, 4, 6 ug / mouse / 100 μl) were administered, and saline (0.9% Saline, 100 μl) were added to chronic stressed mice for 14 days. Group (RST + Veh) administered with nanostress (EV, 2, 4, 6 ug / mouse / 100 μl) for 14 days to mice subjected to chronic stress (RST + EV), and chronic stress After the mice were classified into groups (RST + IMI) administered with imipramine (IMI, 20 mg / kg / day) for 14 days, three kinds of depressive behavior tests were performed in the same manner as in Example 1 above. As it was carried out. In addition, two weeks after the first behavior test (Behavior test-1), the second behavior test (Behavior test-2) was performed in the same order. In addition, when the nanovesicles are injected, the nanovesicles are administered daily from the end of the stress treatment, but from 1 day (p1) to 4 days (p4) until 2 ug / mouse / 100 μl and 5 days (p5) to 6 days (p6) 4 ug / mouse / 100 μl, 7 days (p7) to 14 days (p14) were gradually increased to 6 ug / mouse / 100 μl.

First, as shown in FIG. 6, in the field adaptation period (Habituation), there was no difference in time between the two groups between the mouse groups. However, in the target condition, the stressed control group compared to the control group (CON + Veh) in the target condition. In the case of (RST + Veh), the time spent in the target space was reduced. In contrast, the stress-treated nanovesicles (RST + EV) and imipramine-treated groups (RST + IMI), respectively, were found to return to control levels.

Next, as a result of conducting a tail test and a forced swimming test, respectively, as shown in FIG. 7, in the stressed group (RST + Veh), the immobility was significantly increased compared to the control group (CON + Veh), while stress was increased. It was confirmed that the dead time was reduced to the control level in the group receiving the nanovesicles (RST + EV) and the imipramine group (RST + IMI).

Further, the same behavioral test was performed again two weeks after the first behavioral test of FIGS. 6 and 7, and as shown in FIG. 8, stress was also applied to the secondary test results as well as the first U-BOX test results. In the vesicle-administered group (RST + EV) and imipramine-treated group (RST + IMI), the time spent in the target space was still recovering to a level similar to that of the control group. In addition, as shown in FIG. 9, the secondary tailing test and the forced swimming test results were the same as those of the first experimental results, and the group administered the nanovesicles (RST + EV) and the imipramine were stressed. (RST + IMI) confirmed that the immobility time was reduced to the control level.

The results suggest that the administration of nanovesicles in the mouse model induced depression with chronic stress showed an antidepressant effect.

The description of the present invention set forth above is for illustrative purposes, and one of ordinary skill in the art may understand that the present invention may be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. There will be. Therefore, it should be understood that the embodiments described above are exemplary in all respects and not restrictive.

Lactobacillus plantarum-derived vesicles according to the present invention is stress, anxiety disorder. Useful in the development of medicines or dietary supplements to prevent, ameliorate, or treat mental disorders such as post-traumatic stress disorder, panic disorder, depression, autism spectra disorder, attention deficit hyperactivity syndrome, and schizophrenia Can be.

Claims (20)

1. Lactobacillus plantarum-derived vesicles comprising as an active ingredient, a pharmaceutical composition for the prevention or treatment of mental diseases.
2. The method of claim 1,

   The mental illness is stress, anxiety disorder. Post-traumatic Stress Disorder (PTSD), panic disorder, depression, Autism spectrum disorders, attention deficit / hyperactivity disorder (ADHD), and Pharmaceutical composition, characterized in that the disease is selected from the group consisting of schizophrenia.
3. The method of claim 1,

   The vesicles are characterized in that the average diameter of 10 nm to 1000 nm, pharmaceutical composition.
4. The method of claim 1,

   The vesicles are characterized in that separated from the Lactobacillus plantarum culture, pharmaceutical composition.
5. The method of claim 1,

   The vesicles are characterized in that separated from the food prepared by adding Lactobacillus plantarum, pharmaceutical composition.
6. The method of claim 1,

   The vesicles are characterized in that they are secreted naturally or artificially in Lactobacillus plantarum, pharmaceutical composition.
7. Comprising Lactobacillus plantarum-derived vesicles as an active ingredient, a health functional food composition for improving mental disorders.
8. The method of claim 7, wherein

   The mental illness is stress, anxiety disorder. Post-traumatic Stress Disorder (PTSD), panic disorder, depression, Autism spectrum disorders, attention deficit / hyperactivity disorder (ADHD), and Schizophrenia is a disease selected from the group consisting of health functional food composition.
9. The method of claim 7, wherein

   The vesicles are characterized in that the average diameter of 10 nm to 1000 nm, health functional food composition.
10. The method of claim 7, wherein

    The vesicles are characterized in that separated from the Lactobacillus plantarum culture, health functional food composition.
11. The method of claim 7, wherein

    The vesicles are characterized in that separated from food prepared by adding Lactobacillus plantarum, health functional food composition.
12. The method of claim 7, wherein

    Said vesicles are secreted naturally or artificially in Lactobacillus plantarum, health functional food composition.
13. Lactobacillus plantarum-derived vesicles comprising as an active ingredient, inhalation composition for the prevention or treatment of mental diseases.
14. The method of claim 13,

    The mental illness, the mental illness is stress, anxiety disorder. Post-traumatic Stress Disorder (PTSD), panic disorder, depression, Autism spectrum disorders, attention deficit / hyperactivity disorder (ADHD), and Schizophrenia is a disease selected from the group consisting of, inhalant composition.
15. The method of claim 13,

    The vesicles are characterized in that the average diameter of 10 nm to 1000 nm, inhalant composition.
16. The method of claim 13,

    Said vesicles are separated from the Lactobacillus plantarum culture, inhalant composition.
17. The method of claim 13,

    Said vesicles are separated from food prepared by adding Lactobacillus plantarum, inhalant composition.
18. The method of claim 13,

    Said vesicles are secreted naturally or artificially in Lactobacillus plantarum, inhalant composition.
19. A method for preventing or treating mental disorders, comprising administering to a subject a pharmaceutical composition comprising Lactobacillus plantarum-derived vesicles as an active ingredient.
20. Use for the prevention or treatment of mental illness of Lactobacillus plantarum-derived vesicles.

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