KR101862836B1 - Pharmaceutical composition comprising heracleum moellendorffii hance extract for preventing or treating depression - Google Patents

Abstract

The present invention relates to a pharmaceutical composition and a food composition for alleviating stress diseases comprising a Heracleum moellendorffii extract for preventing or treating stress diseases.

Description

[0001] PHARMACEUTICAL COMPOSITION COMPRISING HERACLEUM MOELLENDORFFII HANCE EXTRACT FOR PREVENTING OR TREATING DEPRESSION [0002]

The invention eosuri (Heracleum moellendorffii The present invention relates to a pharmaceutical composition for the prevention or treatment of a stress-related disease, 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. This long-term over-secretion of glucocorticoids lowers the body's immune system, reducing resistance to external infections and causing a variety of 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 the stress response, have been developed in addition to these antidepressant drugs. However, development of therapeutic agents that can cure depression and neurological diseases caused by stress is still insufficient. In addition, many patients are not responding well to conventional antidepressants, have a high recurrence rate, and are unable to take medications 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.) 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.

Korean Patent No. 10-0798639 Korean Patent No. 10-1313255

An object of the present invention is eosuri (Heracleum moellendorffii The present invention also provides a pharmaceutical composition for preventing or treating a stress disorder,

It is another object of the present invention to provide a food composition for the improvement of a stress disorder comprising an aquatic extract.

According to an aspect of the present invention, there is provided a pharmaceutical composition for preventing or treating a stress disorder, which comprises an extract of Heracleum moellendorffii Hance .

In the present invention, " Heracleum moellendorffii Hance ) is a plant of Umbelliferae, a perennial plant that grows relatively commonly in mountainous areas of Korea. It is said that the root of an aquatic plant is sown in spring and it is planted in spring in October when the leaves are yellowish in July ~ September of the following year. When the leaves are yellowish, they take root and remove stem and root, Muscle aches, arthritis, back pain, and it is also used for treatment of itchy skin, swelling, headache, chills and fever. In the private sector, the young leaves of the aquarius are used for edible purposes, and the fruits and roots are used for the purpose of feces, cold, beauty, and drainage.

The " extract " of the present invention is formed by using not only an extract of an aquarium but also a diluent or concentrate of the extract, a dried product obtained by drying the extract, a preparation or a purified product of the extract, Includes extracts of all possible formulations. The extract may also contain fractionated hexane fractions, chloroform fractions, ethyl acetate fractions, butanol fractions and water fractions after addition of the fractions in the order of fraction solvent, such as hexane, chloroform, ethyl acetate, butanol and water, But is not limited thereto.

The extract of the present invention can be extracted from natural, hybrid, or mutant plants of the respective plants, and can also be extracted from plant tissue cultures.

The method for extracting the extract of the present invention is not particularly limited and may be carried out according to a method commonly used in the art. Non-limiting examples of the extraction method include hydrothermal extraction, ultrasonic extraction, filtration, and reflux extraction. These may be performed alone or in combination with two or more methods.

The kind of the extraction solvent used in the present invention 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 a mixture of two or more of them.

More specifically, water (or distilled water), a mixed solvent of water and a lower alcohol may be used as an extraction solvent in the present invention. A solvent extract can be prepared by extracting the aquarium at least once using the above solvent, and the dry extract obtained by vacuum distillation or spray drying the solvent extract can be prepared.

 In one specific embodiment of the present invention, an aqua extract is prepared using water (or distilled water) (Example 1) or a mixed solvent of water and ethyl alcohol (Example 2).

In order to remove suspended solid particles, the extract of the present invention may be filtered using a filter, for example, nylon or the like, filtered using a freeze filtration method or the like, and then used as it is or may be directly used by freeze drying, hot air drying, spray drying And dried.

In the present invention, the term " stress disorder " may include not only psychological diseases caused by stress such as lethargy, depression, anxiety disorder, boredom but also physical symptoms such as fatigue, indigestion, dyspnea have. Specifically, it may be depression or anxiety disorder.

In one embodiment of the present invention, it was confirmed that an effect of alleviating anxiety was excellent through a general locomotor activity test (Fig. 2). In addition, it was confirmed that the mouse administered with the aquatic extract through the tail suspension test significantly increased the moving time, thereby confirming that the aquatic extract had an antidepressant effect (Fig. 3).

The pharmaceutical composition of the present invention 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. Further, the therapeutic compositions of the present invention may be formulated using methods known in the art or as disclosed in Remington ' s Pharmaceutical Sciences (recent edition), Mack Publishing Company, Easton PA) .

Further, the pharmaceutical composition may further comprise an appropriate carrier, excipient and diluent which are conventionally used in the preparation of a pharmaceutical composition containing an aquatic extract, wherein the aquatic extract is present in an amount of 0.01 to 90% by weight, 0.1 to 50% by weight.

Examples of the carrier, excipient and diluent which may be included 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.

As a base for suppositories, witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like can be used.

The dosage of the composition of the present invention may be appropriately selected or modified depending on the condition and body weight, degree of disease, drug form, administration route and period. Preferably, the therapeutic composition of the present invention may be administered at a dose of 0.0001 to 1000 mg / kg per day based on the amount of the aquatic extract, and preferably 0.01 to 100 mg / kg per day to be more effective. The number of administrations may be administered once a day or divided into several administrations. The dose and the number of administrations do not limit the scope of the present invention in any aspect.

Another aspect of the present invention provides a food composition for improving a stress disorder, comprising an aquatic extract. Specifically, the aquatic extract has antistress and antidepressant effects, as described above.

The food composition means a natural product or a processed product containing one or more nutrients and can be directly eaten through a certain degree of processing. It includes all kinds of health functional foods, beverages, food additives and beverage additives do. The food may further comprise suitable carriers, excipients and diluents conventionally used.

In the present invention, the food composition may specifically be a health functional food. 'Health functional food' means the control of the body's defense rhythm, the prevention of disease and the restoration of the food group or the food composition that has added added value to function and express the function of the food by using physical, biochemical and biotechnological techniques. Refers to foods that are processed and designed so that their body control function is sufficiently expressed in living bodies.

In addition, the 'beverage' in the food composition of the present invention means a generic term for drinking thirst or for enjoying a taste, and includes a health functional beverage. The above-mentioned health functional beverage includes a food group imparted with added value to function or express the function of the food by using physical, biochemical, biotechnological techniques, etc., or a food group which controls the bio- defense rhythm of the food composition, Refers to a beverage that is processed by designing the control function to be sufficiently expressed in living bodies.

The beverage is not particularly limited as long as it contains the aquatic extract as an active ingredient as an essential ingredient at the indicated ratio, and may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages .

Examples of such natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose, sucrose and the like and polysaccharides such as dextrins, cyclodextrins and the like, and Xylitol, sorbitol, and erythritol. Natural flavors (tau martin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above The ratio of the natural carbohydrate may be generally about 1 to 20 g, more specifically 5 to 12 g, per 100 ml of the food composition of the present invention. In addition, the composition of the present invention may be natural fruit juice, fruit juice drink, Of the pulp of the present invention.

In addition to the above, the food or beverage of the present invention may contain flavoring agents such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and aging agents (cheese, chocolate etc.), pectic acid and its salts, And salts thereof, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. These components can be used independently or in combination. The proportion of such an additive may be selected from the range of 0 to 20 parts by weight per 100 parts by weight of the aquatic extract, but is not limited thereto and may be suitably modified and used as necessary.

The aquatic extract of the present invention exhibits excellent anti-stress and anti-depressant effects, but does not affect the exercise function, and thus has excellent safety, and thus can be used as a therapeutic agent for stress-related 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.
FIG. 2 shows the result of the general motility test that evaluated anti-stress and anti-depressant effects.
Figure 3 shows the result of a forced swimming test evaluating the antidepressant effect.

Hereinafter, the present invention will be described in detail by way of examples. However, the following examples are illustrative of the present invention, and the present invention is not limited by the following examples.

Example 1 Preparation of an Aquatic Extract

1-1. Hot water extraction method using water solvent

After drying, 100 g of the ground fishes were added to 1 liter of distilled water, stirred well, and then subjected to reflux extraction at an extraction temperature of 90 to 95 캜 for 3 hours. After that, the filtrate was separated, and the extract was concentrated under reduced pressure at 55 to 65 ° C and then lyophilized to obtain 21.2 g of powdery extract.

1-2. Hot water extraction method using water-alcohol mixed solvent

After drying, 100 g of the ground fishes were mixed with 1 liter of 25% ethyl alcohol and stirred well. The mixture was heat-refluxed at an extraction temperature of 80 to 90 ° C for 3 hours. After that, the filtrate was separated, and the extract was concentrated under reduced pressure at 55 to 65 ° C and then lyophilized to obtain 19.5 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, Jungwon-dong, Jungwon-gu, Seongnam-si, Gyeonggi-do) and used for adaptation for more than one week in Kyunghee Medical Center animal feeding room. Water and feed were freely consumed , Temperature (23 ± 2 ° C), humidity (55 ± 10%) and light intensity were automatically adjusted at intervals of 12 hours. For each experiment, 10 to 12 mice per group were used.

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 in Experimental Example 3 and Experimental Example 4 were carried out by placing 10 mice in the sham control, the negative control, the experimental group A and the experimental group B, respectively.

Sham control was injected only with water after Sharm surgery, negative control, and experimental group A and experimental group B induced depression with L-AAA. Then, water was orally administered to the negative control group, and 200 mg / kg of the avian extract (KH019 in the figure) was administered to the experimental group A and 500 mg / kg of the avian extract was administered to the experimental group B.

Experimental Example 3: Open field test

In order to evaluate the basic motility and movement of mice, 10 mice were assigned to each of Sham control, Negative control, Experimental group A and Experimental group B and a general motility test was performed.

Each mouse corresponding to Sham control, Negative control, Experimental group A and Experimental group B was placed in a 50 × 50 × 50 cm white acrylic box and the video tracking system (smart v.2.5. 21) for 10 min. The open field was divided by 9 and the central zone was set as the central zone. Then, the amount of gait activity using the spontaneous momentum of each group was measured, and the results are shown in FIG.

As shown in FIG. 1, no significant difference was observed in the simulated control, negative control, experimental group A, and experimental group B, respectively. This indicates that there was no change in the amount of gait activity due to the drug administration. It was confirmed that the gait extract did not affect the amount of gait activity. In addition, the reliability of the subsequent experimental results is secured.

In addition, the open field was divided into nine equal parts, the middle zone was set as the central zone, and the anticipatory and antidepressant effects were confirmed by measuring the anxiety behavior using the time spent in the central zone and the number of times of entry. The anxiety symptom was alleviated with a higher number of mouse entry into the central zone. The lower the entry number, the more anxiety was evaluated. The results are shown in FIG.

As shown in FIG. 2, in the case of the experimental group B, the entry into the middle region was remarkably high and it was found that the effect of relieving anxiety was excellent. From these results, it was confirmed that anti-stress and anti-depressant effects were excellent.

Experimental Example 4 Tail Suspension Test (TST)

In order to confirm the antidepressant effect of the aquatic extracts, a 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 photographed for 6 minutes using a digital camera, the time for which the mouse was moved for 6 minutes, and the result is shown in FIG.

As shown in FIG. 3, in the experimental group B, the moving time was significantly increased as compared with the negative control group, and it was found that the antidepressant effect of the aqua extract was excellent.

Through the above experiments, it was confirmed that the aquatic extract of the present invention exhibits antistress and antidepressant effects, and thus it can exhibit a therapeutic and improving effect on stress diseases, especially depression and anxiety disorders.

This indicates that the composition of the present invention can be used as a therapeutic agent for alcoholic brain nervous system diseases and as a food for improvement and further can be used as a composition for relieving hangover since it can improve cognitive power reduced by alcohol will be.

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 pharmaceutical composition for preventing or treating depression or anxiety disorder comprising an extract of Heracleum moellendorffii Hance . delete The pharmaceutical composition according to claim 1, wherein the aquatic extract is extracted from water or a mixed solvent of water and ethanol. A food composition for improving depression or anxiety disorders, comprising an aquatic extract. delete 5. The method of claim 4,
Wherein the food composition is a health functional food.

Images