KR20190016754A - A pharmaceutical composition comprising tetragonia tetragonoides extract for preventing or treating depression - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating a stress-related disease, including a tetragonia tetragonoides extract exhibiting excellent anti-stress and anti-depression effects, and to a food composition for relieving a stress-related disease. The pharmaceutical composition for preventing or treating a stress-related disease comprises a tetragonia tetragonoides extract as an active ingredient, wherein the tetragonia tetragonoides extract is extracted with water, a C1 to C4 lower alcohol, or a mixed solvent thereof.

Description

TECHNICAL FIELD [0001] The present invention relates to a pharmaceutical composition for preventing or treating a stress disorder,

The present invention relates to a pharmaceutical composition for the prevention or treatment of a stress-related disease comprising an effective amount of an early extract, and a food composition for improving a stress-related disease.

Modern industrial society is changing rapidly and complexly structurally and functionally. In addition, there is an enormous amount of information coming out daily, which is difficult for an individual to digest. Most of the modern people who have to adapt to new technology and new environment feel a lot of physical and psychological burden. This stress is called stress.

The body's acceptable levels of stress will act as an appropriate stimulant for our body, but strong and persistent psychological and physical stresses outside the acceptable range induce hyperglycemia of glucocorticoids for prolonged periods of time.

Glucose corticosteroids, which are over-secreted for a long period of time, lower the body's immune system, thus reducing resistance to external infections and causing various diseases in our bodies. In addition to diminishing immunity, it also inhibits brain cell damage and regeneration, resulting in insomnia, lethargy, memory loss, depression, as well as suicide.

A variety of antidepressant drugs such as Prozac, Zoloft, Serzat, Ipasa, and Remeron, which are now known as serotonin reuptake inhibitors, have been developed, including tricyclic drugs developed in the 1960s as therapeutic agents for the treatment of depression. In addition, CRH receptor antagonists that bind CRH, the first substance of stress response, have been developed in addition to antidepressant drugs.

However, the development of therapeutic agents that can cure depression and neurological diseases due to stress has not been developed yet. Many patients are not responding well to conventional antidepressants, have a high recurrence rate, and are unable to take medication due to severe side effects.

Tricyclic antidepressants (TCAs) such as imipramine and desipramine have been associated with severe side effects such as hypotension and cardiac dysfunction, and the most commonly used fluoxetine or sertraline sertraline, etc.) may cause zone, gastrointestinal bleeding or sexual dysfunction.

In addition, antidepressants usually lead to long-term use. Chemotherapeutic agents are very frequently used for long-term side effects and toxicity, so they are interested in research to search for new therapeutic agents that can treat diseases effectively and harmlessly to humans. .

However, since there is no side effect as a natural material and safety is recognized, the present invention is still not satisfactory in terms of improving or treating depression, and accordingly, development of a new technology for meeting the continuous demand for therapeutic agents using natural extracts Is required.

It is an object of the present invention to provide a pharmaceutical composition for the prevention or treatment of a stress disorder comprising Tetragonia tetragonoides extract.

It is another object of the present invention to provide a food composition for the improvement of a stress disorder comprising a pre-emergence herb extract.

According to one aspect of the present invention, there is provided a cranial nerve protecting composition comprising Tetragonia tetragonoides extract as an active ingredient.

In one embodiment, the extract may be extracted with water, C1 to C4 lower alcohols, or a mixed solvent thereof.

According to another aspect of the present invention, there is provided a pharmaceutical composition for preventing or treating a stress disorder comprising the composition as an active ingredient.

In one embodiment, the stress disorder can be selected from the group consisting of a depressive disorder, a sleep disturbance, and an anxiety disorder.

According to another aspect of the present invention, there is provided a health functional food for preventing or ameliorating a stress disorder comprising the composition as an active ingredient.

In one embodiment, the stress disorder can be selected from the group consisting of a depressive disorder, a sleep disturbance, and an anxiety disorder.

The novel herb extract of the present invention exhibits excellent anti-stress and anti-depressive effects, and at the same time does not affect the exercise function and is thus excellent in safety, so it can be used as a therapeutic agent for stress diseases and as a food for improvement.

It should be understood that the effects of the present invention are not limited to the effects described above, but include all effects that can be deduced from the description of the invention or the composition of the invention set forth in the claims.

FIG. 1 shows the results of the general motility test that evaluated the amount of gait activity.
Figure 2 is an evaluation of antidepressant activity following drug administration in the sucrose preference test (SPT).
FIG. 3 is an evaluation of antidepressant activity according to drug administration in forced swimming test (FST).
Figure 4 shows the antidepressant activity following drug administration in the tail suspension test (TST).

As used herein, the terminology used herein is intended to encompass all commonly used generic terms that may be considered while considering the functionality of the present invention, but this may vary depending upon the intent or circumstance of the skilled artisan, the emergence of new technology, and the like. Also, in certain cases, there may be a term selected arbitrarily by the applicant, in which case the meaning thereof will be described in detail in the description of the corresponding invention. Therefore, the term used in the present invention should be defined based on the meaning of the term, not on the name of a simple term, but on the entire contents of the present invention.

Unless defined otherwise, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Terms such as those defined in commonly used dictionaries are to be interpreted as having a meaning consistent with the contextual meaning of the related art and are to be interpreted as either ideal or overly formal in the sense of the present application Do not.

The numerical range includes numerical values defined in the above range. All numerical limitations of all the maximum numerical values given throughout this specification include all lower numerical limitations as the lower numerical limitations are explicitly stated. All the minimum numerical limitations given throughout this specification include all higher numerical limitations as the higher numerical limitations are explicitly stated. All numerical limitations given throughout this specification will include any better numerical range within a broader numerical range, as narrower numerical limitations are explicitly stated.

Hereinafter, embodiments of the present invention will be described in detail, but it should be apparent that the present invention is not limited by the following examples.

One aspect of the present invention provides a cranial nerve protecting composition comprising Tetragonia tetragonoides extract as an active ingredient.

The above-mentioned " Tetragonia tetragonoides " is also referred to as "ginseng lettuce", "ginseng spinach", "New Zealand spinach", "bamboo bamboo", and "white pine", and its origin is a perennial plant of Aizoaceae.

It is distributed in New Zealand, China, Japan, South Asia, Australia, and South America. South Korea is growing in the seaside sandy areas of South and Jeju Island. It has been known as a herb as a herb since ancient times, and is known as the three great medicinal herbs in the stomach, along with the herb of the mountain, the 'roots of leaves', and the'

Recently, the efficacy of prophylactic treatment for the prevention and treatment of gastrointestinal diseases is known, and the herbal medicine treats it as a valuable drug used for the treatment of gastrointestinal diseases such as cancer, gastritis, gastric ulcer, gastric hyperplasia and indigestion. Depressive activity is not yet known.

The type of the solvent in the above-mentioned extraction process is not particularly limited, and the solvent may be varied if necessary. In addition, the extraction can be carried out using a conventional method in the art such as cold-rolling, warming, heating, and the like using the solvent.

The type of the extraction solvent is not particularly limited, and any solvent known in the art can be used. Non-limiting examples of the extraction solvent include water, anhydrous or lower alcohol of C ₁ to C ₄ , a mixed solvent of water and lower alcohol, acetone, 1,3-butylene glycol, ethyl acetate, chloroform Or more.

When ethanol is used as the extract solvent, not only the stability can be enhanced but also it is harmless to the human body, so it can exhibit excellent suitability for use as a food or pharmaceutical composition, and the cost increase such as strict process control for securing stability The economic effect can also be improved.

The extract may be extracted from natural, hybrid or variant plants of the respective plants, and may be extracted from plant tissue cultures.

The extraction method is not particularly limited and may be carried out according to a method commonly used in the art. Examples of the extraction method include a hot water extraction method, an ultrasonic extraction method, a filtration method, and a reflux extraction method. These methods may be performed alone or in combination of two or more methods.

The extract may be filtered to remove suspended solid particles, for example, by filtration using nylon or the like, or by filtration using a freeze filtration method or the like, or the extract may be used as it is or may be dried by freeze drying, hot air drying, Can be used.

According to another aspect of the present invention, there is provided a pharmaceutical composition for preventing or treating a stress disorder comprising the composition as an active ingredient.

The term " stress disease " refers to a condition in which the function of the autonomic nervous system and neuroendocrine system is changed by internal and external stimuli commonly used as stress, and the degree of such change is exceeded or maintained for a long period. ≪ / RTI >

The above-mentioned " stress-related diseases " may include all kinds of psychological diseases caused by stress, for example, lethargy, depression, anxiety disorder, boredom as well as physical symptoms such as fatigue, indigestion, dyspnea, A depressive disorder, a sleep disturbance, or an anxiety disorder.

According to recent research results, stress-related diseases can also be caused by neuronal cell damage, and the neuron protective composition can be effectively used as a preventive or therapeutic use against stress diseases due to excellent neuronal cell-borne effect.

Said " prophylactic " means a reduction in the degree of pathological cell development or damage or loss of an animal. Prevention can be complete or partial. In this case, it may mean that the possibility of the occurrence of a stress disease due to the development of pathological cells in an individual or the death or loss of nerve cells may be reduced.

The " treatment " means improving one or more symptoms of a stress disorder, inhibiting the progress of symptoms, and may encompass the meaning of commonly used treatments.

The pharmaceutical composition may be a granule, a powder, a syrup, a liquid, a suspension, an agent, an infusion, a tablet, a suppository, an injection, a main tablet, a capsule, a pill, a soft or hard gelatin capsule and the like. The pharmaceutical compositions may be formulated using any suitable method known in the art or using methods disclosed in Remington's Pharmaceutical Science (recent edition), Mack Publishing Company, Easton PA.

In the preparation of the pharmaceutical composition, it may further comprise suitable carriers, excipients and diluents conventionally used.

Examples of carriers, excipients and diluents that can be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, it can be prepared using diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, surfactants and the like which are usually used.

Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose ) Or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used.

Examples of liquid formulations for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, .

Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like.

Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The dosage of the pharmaceutical composition may be suitably selected or modified depending on the condition and body weight, degree of disease, drug form, administration route and duration. Preferably, the pharmaceutical composition may be administered at a dose of 0.0001 to 1000 mg / kg / day, more preferably 0.01 to 100 mg / kg / day, based on the amount of the first-time extract. The administration frequency may be administered once a day or divided into several doses, but the scope of the present invention is not limited by the dosage and the number of administrations.

According to another aspect of the present invention, there is provided a health functional food for preventing or ameliorating a stress disorder comprising the composition as an active ingredient. Specifically, the progeny extract has antistress and antidepressant effects as described above.

The food means a natural product or a processed product containing one or more nutrients. The food can be exemplified by meat, snack, dairy product, beverage, and the like, but is not limited thereto, and can be understood as a concept including all common health functional foods.

The health functional food refers to a food prepared and processed by using raw materials or ingredients having useful functions in the human body according to the Act on Health Functional Foods. The functional properties include nutrients for the structure and function of the human body, ≪ / RTI > may be meant to be ingested for the purpose of obtaining a beneficial effect for a health use such as the action.

The above-mentioned health functional foods may contain usual food additives, and the above food additives may be added to the standards and standards of the relevant items in accordance with the General Rules for Food Additives approved by the Food and Drug Administration and the General Test Methods, It can be judged whether it is suitable or not.

The food additives described in the above-mentioned Food Additives Code include chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid, natural additives such as persimmon extract, licorice extract, crystalline cellulose, high- A preservative formulation, a tar coloring agent, and the like.

The health functional food can be used for various foods and beverages for improving stressful diseases and can be used for various foods, beverages, gums, tea, vitamin complex, health functional auxiliary food, food additive and the like.

The health functional food may contain 1.0 to 10.0% by weight of the first-time extract for the purpose of improving the stress-related diseases. If the content of the extract is less than 1.0% by weight, the effect of improving the stress-related disease may not be sufficiently realized. If the content is more than 10.0% by weight, the quality of the product may not be realized or the cost efficiency may be deteriorated.

The health functional food may be manufactured and processed into any one form selected from the group consisting of tablets, granules, powders, capsules, liquid solutions and rings for the purpose of improving a stressful disease.

Specifically, the health functional food of the tablet form may be prepared by granulating a mixture of the brain protecting composition, the excipient, the binder, the disintegrating agent and other additives in a conventional manner, and then compressing the mixture by a lubricant or the like, Followed by compression molding. The health functional food of the tablet form may contain a mating agent and the like if necessary, and may be sieved to a suitable skin care agent if necessary.

The hard capsule of the above-mentioned capsule type health functional food can be prepared by filling a normal hard capsule with a mixture with the above-mentioned cranial nerve protecting composition and an additive such as an excipient, or a granular material thereof or a gelatinized granular material. A preservative composition, and an excipient such as an excipient into a capsule base such as gelatin. The soft capsule may contain a plasticizer such as glycerin or sorbitol, a coloring agent, a preservative and the like, if necessary.

The above-mentioned ring-form health functional food can be prepared by molding a mixture of the above-mentioned cranial nerve-protecting composition, excipient, binder, disintegrant and the like by an appropriate method. If necessary, the preparation may be mixed with saccharide or other suitable skin- It may also be an objectionable substance.

The above-mentioned granular form of health functional food may be prepared by granulating the above-mentioned composition for protecting nervous system, excipient, binder, disintegrant and the like by a suitable method, and if necessary, may contain a flavoring agent, a mating agent and the like.

Further, the definitions of the above excipients, binders, disintegrants, lubricants, mating agents, flavoring agents and the like are described in documents known in the art, and the functions and the like may be the same or similar.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings, but it should be apparent that the present invention is not limited by the following embodiments.

Preparation Example: Preparation of Novel Leaf Extract

Hot water extraction method using water solvent

Drying, Milling 600 g of the first step was added to 3 liters of distilled water, stirred well, and then refluxed for 3 hours at an extraction temperature of 90 to 95 ° C. The filtrate was separated, and the extract was concentrated under reduced pressure at 55 to 65 ° C and then lyophilized to obtain 91 g of powdery extract.

Hot water extraction method using water-alcohol mixed solvent

After drying and pulverization, 600 g of 35% ethyl alcohol was added to 3 L of agitation, followed by reflux extraction at an extraction temperature of 80 to 90 ° C for 3 hours. The filtrate was separated, and the extract was concentrated under reduced pressure at 55 to 65 ° C and then lyophilized to obtain 91 g of powdery extract.

Experimental Example 1: Preparation of experimental animals

Seven-week-old C57BL / 6 male mice were supplied from Orient Bio Co., Ltd. (143-1, Joongwon-dong, Jungwon-gu, Seongnam-si, Gyeonggi-do) and reared and adapted for more than a week at the animal breeding room (Kyunghee Medical Center). Water and feed were freely available and temperature (23 ± 2 ° C), humidity (55 ± 10%) and contrast were automatically adjusted at 12-hour intervals. Ten mice per group were used in each experiment.

Experimental Example 2: Production of an animal model of L-AAA induced depression

A depressive mouse model was constructed by injecting L-AAA, a specific toxic substance in astrocytic cells, into the preliminary cortex of the mouse brain to report depression by eliminating locally specific astrocytes (Banasr M , Duman RS, Glial loss in the prefrontal cortex is sufficient to induce depressive-like behaviors. Biol Psychiatry 2008 Nov 15; 64 (10): 863-870).

A guide cannula was inserted and fixed before injection of L-AAA, and L-AAA was injected twice on both sides of the cerebral hemisphere to prepare a depression model.

The experiments performed below were carried out with 10 mice in each of the sham control, negative control, positive control and experimental group.

Sham control was injected only with water after Sharm surgery, and negative control, positive control, and experimental group induced depression with L-AAA. Thereafter, water was orally administered to the negative control group, imipramine was administered to the positive control group, and oral administration of 100 mg / kg and 300 mg / kg of the pre-emergence herb extract, respectively.

Experimental Example 3: Open field test

In order to evaluate the basic motility and movement of the mouse, 10 mice were assigned to each of the sham control, negative control, positive control and experimental group, and a general motility test was performed.

The mouse was placed in a 50 × 50 × 50 cm white acrylic box and the behavior was measured for 10 minutes using a video tracking system (smart v.2.5.21). The open field was divided by 9 zone. After that, the amount of gait activity using the spontaneous momentum of each group was measured (Fig. 1)

Referring to FIG. 1, no significant differences were observed in the simulated control group, the negative control group, the positive control group, and the experimental group. The above results indicate that there is no change in the amount of gait activity due to the administration of the drug, and the problem of the gait function was not caused by the administration of the drug. Especially, the gait extract had no effect on the gait activity. As a result, the reliability of the subsequent experimental results is secured.

Experimental Example 4: Sucrose preference test (SPT)

Mice were adapted to 0.1 M sucrose and water for 48 hours. Two bottles were placed in the cage, which were identical in shape and indistinguishable, and water and 0.1 M sucrose were added, respectively.

Water and food were removed from the cage for 12 hours after 48 hours of sucrose habituation (deprivation period).

After 12 hours, water and 0.1 M sucrose were added to the cage, respectively, and the same amount of water and 0.1 M sucrose were measured for 6 hours (FIG. 2).

Sucrose preference was calculated by the following equation 1, and sucrose preference decreased when depressed.

[Formula 1]

Sucrose preference (%) = sucrose intake / (water intake + sucrose intake)

Experimental results showed that sucrose affinity was increased in the experimental animal model of depression induced by L-AAA, and higher sucrose preference was increased compared to imipramine used as an antidepressant Effect.

Experimental Example 5: Forced swim test (FST)

The anti-depressive activity of the green tea extract (preparation example) was confirmed by a forced swimming test of the mouse.

Specifically, a cylinder having a diameter of 20 cm and a depth of 35 cm was filled with 20 cm of water at 24 1 C to prevent the tail of the mouse from touching the bottom of the cylinder. The mice were each administered a sample of the preparation example or a control group, and after 1 hour, the mouse was put in a cylinder and then recorded by using a digital camera for 6 minutes.

Forced swimming mice seem to alternate between activity and immobility time. Anti-depressants decrease the time of immobility (floating time) in a dose-dependent manner.

During the remaining 4 minutes except for the initial 2 minutes in the recorded video, the time when the mouse was put on the surface of the head and kept still without movement was measured (Fig. 3).

Experimental results showed that the immobilization time was significantly reduced when the preparation sample was administered to an animal model in which depression was induced by L-AAA, and a higher level of immobilization time was reduced compared to imipramine used as an antidepressant Effect.

Experimental Example 6: Tail Suspension Test (TST)

In order to investigate the antidepressant effect of the extract of Pseudomonas spp., Tail suspension test was performed on the mouse.

Specifically, an anti-depressant activity was evaluated by measuring the moving time of the mouse by attaching a tape having a high adhesive strength to the edge of 45 cm in height at 1 to 2 cm of the tail end of the mouse and suspending the mouse. The movement of the mouse was taken for 6 minutes using a digital camera and the time the mouse was moved for 6 minutes (Figure 4)

Referring to FIG. 4, in an animal model in which depression was induced by L-AAA, the immobilization time was reduced when the preparation sample was administered, and a higher level of immobility compared to the imipramine, Time reduction effect.

The above results suggest that the first-time extracts exhibit anti-stress and anti-depressant effects, and thus may exhibit therapeutic and ameliorative effects on stress-related diseases, particularly depression and anxiety disorders.

It will be understood by those skilled in the art that the foregoing description of the present invention is for illustrative purposes only and that those of ordinary skill in the art can readily understand that various changes and modifications may be made without departing from the spirit or essential characteristics of the present invention. will be. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive. For example, each component described as a single entity may be distributed and implemented, and components described as being distributed may also be implemented in a combined form.

The scope of the present invention is defined by the appended claims, and all changes or modifications derived from the meaning and scope of the claims and their equivalents should be construed as being included within the scope of the present invention.

Claims (6)

A composition for protecting cranial nerves comprising an extract of Tetragonia tetragonoides as an active ingredient. The method according to claim 1,
Wherein the extract is extracted with water, C1 to C4 lower alcohols, or a mixed solvent thereof. A pharmaceutical composition for preventing or treating a stress disorder comprising the composition of claim 1 or 2 as an active ingredient. The method of claim 3,
Wherein said stress disorder is selected from the group consisting of depressive disorder, sleep disturbance, and anxiety disorder. A health functional food for preventing or ameliorating a stress disorder comprising the composition of claim 1 or 2 as an active ingredient. 6. The method of claim 5,
Wherein said stress disorder is selected from the group consisting of depressive disorder, sleep disturbance, and anxiety disorder.

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