KR20180097094A - A composition comprising valeriana fauriei briquet extract for treating neurodegenerative disease - Google Patents

Abstract

An embodiment of the present invention provides a composition for the prevention or treatment of degenerative brain diseases containing a Valeriana fauriei Briquet extract as an effective component.

Description

TECHNICAL FIELD [0001] The present invention relates to a composition for treating degenerative brain diseases, which contains an extract of Ganoderma lucidum as an active ingredient. BACKGROUND ART [0002]

The present invention relates to a composition for preventing and treating degenerative brain diseases containing a natural extract as an active ingredient.

Recent changes in living environment and eating patterns have caused modern people to be interested in degenerative neurological diseases including aging of living tissues. In particular, with the rapid increase in the elderly population, degenerative neurological diseases including brain, spinal, and peripheral nerve damage are increasing. Degenerative nerve diseases include diseases related to nerve injury caused by ischemia and nerve injury caused by reactive oxygen species.

Neurons undergo constant cell death in the process of reconstitution and synapse reconstitution, and stress and apoptotic cell death are major contributors to degenerative neurological diseases. Oxidative stress is known to be related to the cause of degenerative neurological diseases. Recent studies have shown that chronic stress and oxidative stress are related to hypothalamic-pituitary-adrenal hyperplasia, hippocampus, striatum, Induced oxidative stress, leading to increased apoptosis and decreased neuronal and growth factors, leading to degenerative neuropathy.

Free radicals liberated from oxygen are known to be the major cause of tissue damage. Oxidative radicals associated with neurotoxicity include hydrogen peroxide, hydrogen peroxide anion, and hydroxyl group, and hydrogen peroxide is considered to be the most important substance in inducing apoptosis of the central nervous system.

In neuronal cells, reactive oxygen species (Reactive Oxygen Species) are produced by oxidative stress, which causes cytochrome C release and caspase-3 activation in mitochondria, leading to apoptosis. At the same time active oxygen is glutamate, in particular NMDA receptor activation to cause an increase in Ca ²⁺ ions according to the metabolic syndrome tropical cascade (metabotrophical cascade), and the cells increase in the Ca ^{2 +} is to enable the caspase -2 DNA .

The proportion of the elderly population worldwide is increasing gradually. In Korea, the proportion of the population aged 65 or over has risen to 11% in 2010, and it is expected that the aged society will become an aged society in 2018 and the aged society in 2026, .

In particular, Alzheimer's disease, which accounts for about half of senile dementia diseases, currently has no effective treatment and preventive measures, and is a neurological disorder that needs urgent resolution in an aging society.

However, a variety of degenerative neurological diseases such as cell transplantation and surgical operation have risks and side effects, and a therapeutic agent that substantially protects neuronal damage due to the complexity of damage mechanism has not been developed.

Tissue plasminogen activator is a FDA-approved therapeutic agent for cerebral ischemia. It is a thrombolytic agent that dissolves thrombus causing cerebral ischemia and induces rapid supply of oxygen and glucose. However, the tissue plasminogen activator does not directly protect nerve cells, and therefore, it is required to be used promptly. In the case of excessive use or frequent use, the blood vessel wall becomes thin, which may lead to hemorrhagic cerebrovascular disease.

In addition, MK-801 is known to effectively inhibit the initial intracellular calcium influx and thereby inhibit glutamate-induced cytotoxicity. However, side effects have been discovered and discarded as a result of clinical trials.

In Korea, many natural substances are marketed as health foods effective for the prevention of stroke, but many of them have not undergone scientific validation and are considered to be the cause of abuse of health food.

Regarding such degenerative brain diseases, there are no fundamental therapeutic agents to date, and even therapeutic agents that temporarily inhibit the progression of the disease have a limitation due to a decrease in the drug efficacy and various side effects due to the worsening of the disease.

On the other hand, herbal medicines mainly used in Oriental medicine are becoming more fundamental therapeutic agents by multi-target mechanism in the prevention and treatment of chronic and intractable diseases in which causes and symptoms are complex.

In addition, therapeutic agents using such herbal medicines as raw materials are attracting attention as substitutes for existing pharmaceutical ingredients because they can minimize various side effects that may occur depending on the use of chemicals.

Disclosure of Invention Technical Problem [8] Accordingly, the present invention has been made keeping in mind the above problems occurring in the prior art, and it is an object of the present invention to provide a composition containing a natural component to minimize side effects and improve neurodegenerative diseases.

It is another object of the present invention to provide a health functional food for the treatment of neurodegenerative degeneracy comprising the components derived from natural products.

According to an aspect of the invention, the road chogeun (Valeriana fauriei A pharmaceutical composition for preventing or treating degenerative brain diseases comprising Briquet extract as an active ingredient is provided.

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

In one embodiment, the degenerative brain disease is selected from the group consisting of dementia, Alzheimer's disease, stroke, cerebral infarct, head trauma, cerebral arteriosclerosis, Parkinson ' s disease. ≪ / RTI >

According to another aspect of the present invention, there is provided a health functional food for preventing or ameliorating a degenerative brain disease comprising an extract of Ganoderma lucidum as an active ingredient.

According to another aspect of the present invention, there is provided a pharmaceutical composition for protecting cranial nerves comprising an extract of Corynebacterium glutinosa as an active ingredient.

According to one aspect of the present invention, a ginseng root extract, which is a natural herb medicine, is used as a component of a pharmaceutical composition or a health functional food, thereby having excellent biosafety and nerve cell protection effect.

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.

Figure 1 shows the result of observing the basic motility and movement of the mouse.
FIG. 2 is a result of evaluating the spontaneous change action force of a mouse through a Y-maze test.
FIG. 3 shows the result of evaluating the improvement effect of short-term memory disorder in Alzheimer-induced mice through Morris water maze test.

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.

A pharmaceutical composition for the prevention or treatment of degenerative brain diseases according to one aspect of the present invention is provided by Valeriana fauriei Briquet ) extract as an active ingredient.

The term " neurodegenerative disease " refers to a disease occurring in the brain, among neurodegenerative diseases caused by age. Although the cause of degenerative brain disease has not been clearly elucidated, the specific brain cell group of the brain and spinal cord gradually loses its function, and the neuronal cell death that plays a key role in the transmission of the brain nervous system information, , The formation of synapses or functional problems, and the ideal increase or decrease of brain potentials.

The degenerative brain disease can be classified according to the major symptom and the damaged area of the brain, and typical examples thereof include Alzheimer's disease and Parkinson's disease.

Specifically, the degenerative brain disease is selected from the group consisting of dementia, Alzheimer's disease, stroke, cerebral infarct, head trauma, cerebral arteriosclerosis, and Parkinson's disease. disease, and the like. However, the present invention is not limited thereto.

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, the occurrence of pathological cells or death or loss of nerve cells in an individual may be reduced as compared with the case where the composition for preventing and treating neurodegenerative diseases is not used.

The term " treatment " refers to ameliorating one or more symptoms of a degenerative neurological disorder, or inhibiting the progression of symptoms, and may encompass the meaning of commonly used treatments.

The " Valeriana & fauriei Briquet "is a word that comes from one room and is called the root hill or mare urine. Edema, boils, postpartum symptoms and burns, and is mainly used as herbal medicines. Leaves are small, short petiole, petioleous, and split into small leaves. The leaf is narrow underneath, and the tip is sharp or coarse and has coarse saw teeth. The flowers bloom in pale red color, and the ferns gather at the end of the stem. It is distributed in Jeju Island and Geoje Island. It grows in mountainous region.

The present inventors newly elucidated the neuroprotective effect of the herbal extracts. The extracts of the herbal extracts were obtained from neurotoxic substances such as 6-OHDA (6-hydroxydopamine) and LPS (lipopolysaccharide) amyloid-beta Thereby improving the degenerative brain disease.

Unlike the artificial compound, the extract is used as it is, so that it is possible to minimize the occurrence of side effects due to ingestion or administration thereof.

On the other hand, the kind of the solvent in the extraction step 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 extract may be extracted with water, C1 to C4 lower alcohols, or a mixed solvent thereof, preferably ethanol, more preferably 70% ethanol, but is not limited thereto.

When ethanol is used as the extraction solvent, not only the stability can be enhanced but also it is harmless to the human body. Therefore, 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 composition may further comprise carriers, excipients and diluents used in the preparation of conventional pharmaceutical compositions.

Examples of the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, But are not limited to, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil.

In addition, the composition may be formulated in the form of oral, granule, tablet, capsule, suspension, emulsion, syrup, aerosol or the like, external preparation, suppository and sterilized injection solution.

The solid preparations for oral administration include tablets, pills, powders, granules, capsules and the like. These solid preparations may contain at least one excipient such as starch, calcium carbonate, sucrose, Lactose, or gelatin. In addition to the above excipients, lubricants such as magnesium stearate and talc may also be used.

Examples of the liquid preparation for oral administration include suspensions, solutions, emulsions, syrups, and the like. In addition to water and liquid paraffin, simple diluents, various excipients such as wetting agents, sweeteners, have.

The preparation for parenteral administration may be a sterilized aqueous solution, a non-aqueous solvent, a suspension, an emulsion, a lyophilized preparation, or a suppository. Examples of the non-aqueous solvent and suspensions may include injectable esters such as propylene glycol, polyethylene glycol, vegetable oil such as olive oil and ethyl oleate. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, and glycerogelatin.

The pharmaceutical composition comprising the extract may be administered to a subject in a pharmaceutically effective amount. 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 dosage level will depend on the type of disease, severity, activity of the drug, Sensitivity, time of administration, route of administration and rate of excretion, duration of treatment, factors including co-administered drugs, and other factors well known in the medical arts.

The pharmaceutical composition may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or in multiple doses. It is desirable to administer an amount that allows for all of the above factors to be maximally effected in a minimal amount without side effects, which can be readily determined by one skilled in the art.

Another aspect of the invention is the way chogeun (Valeriana fauriei The present invention provides a health functional food for preventing or ameliorating a degenerative brain disease containing an extract of Briquet as an active ingredient.

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 a raw material or a component having a useful function in the human body according to the Health Functional Food Act No. 6727. The functional property refers to the nutrient Or for the purpose of obtaining a beneficial effect for health use such as physiological 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 may be used for various foods and beverages for improving degenerative brain diseases. For example, the health functional food may be used in various foods, beverages, gums, tea, vitamin complex, health functional supplement, food additive and the like.

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 degenerative brain diseases.

Specifically, the health functional food in the form of tablets may be prepared by granulating a mixture of Gill roots extract or its fractions, excipients, binders, disintegrants, and other additives by a conventional method, followed by compression molding with a lubricant or the like, Can be produced by direct 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 capsule type health functional food can be prepared by filling a normal hard capsule with a mixture with an additive such as eggplant extract and excipient, or by granulating or granulating the granule or granule with the soft capsule. Fractions thereof, and excipients such as excipients 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-type health functional food can be prepared by molding a mixture of Giller Root Extract or its fractions, excipients, binders, disintegrants and the like by an appropriate method. If necessary, it may be formulated into white sugar or other suitable skin care agent, Talc or a suitable substance may be used.

The above granular health functional food may be prepared by granulating a mixture of Gil root root extract or fractions thereof, an excipient, a binder, a disintegrant and the like by a suitable method and, if necessary, 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.

Another aspect of the present invention is the way chogeun (Valeriana fauriei Briquet ) extract as an active ingredient. The action, effect, and additional components of the above-described pharmaceutical composition are as described above.

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.

Manufacturing example  One : Gill Heat number  Extract preparation

Gangwon - do harvested from Youngwol in Gangwon - do were dried and used in the experiment. After drying, 100 g of crushed gill root was added to 1 liter of distilled water, refluxed at 90 to 95 ° C for 3 hours, and the filtrate was separated. The herbal medicine extract was concentrated under reduced pressure at 55 to 65 캜, and then lyophilized to obtain 21.2 g of herbal composition powder extract.

Manufacturing example  2 : Gill  Ethanol extract preparation

Gangwon - do harvested from Youngwol in Gangwon - do were dried and used in the experiment. After drying, 100 g of crushed gill root was added to 1 liter of ethanol (25% w / w), refluxed for 3 hours at 90 to 95 ° C, and the filtrate was separated. The herbal medicine extract was concentrated under reduced pressure at 55 to 65 占 폚, and then lyophilized to obtain 19.5 g of herbal composition powder extract.

Experimental Example  1: Open field test

General motility activity tests were performed to observe the basic motility and movement of the mice.

An amyloid beta -42 infused mouse model was constructed for the above test.

C57BL / 6 mice were anesthetized with a 2: 1 mixture of Zoletil and Rumun, followed by injections of amyloid beta1-42 peptide in the hippocampal CA1 region of the brain (coordinates: -2.3 mm anterior / posterior, ± 1.8 mm medial / lateral and -1.75 mm dorsal / ventral from Bregma) nerve damage (Alzheimer).

The mice were placed in a white acrylic box (50 × 50 × 50 cm) and observed for 10 minutes using a video tracking system (smart v.2.5.21). The open field was divided into nine equal parts Was set as the central zone.

Donepezil 1 mg / kg, Gil root extract 200 mg / kg, 600 mg / kg, or distilled water as a control group was administered to the Alzheimer-induced mice, and the amount of gait activity was measured using spontaneous momentum.

There was no significant difference in the amount of gait activity induced by Alzheimer's, and there was no significant difference in the amount of gait activity after administration of the distilled water or gil root extract compared to the animal model without Alzheimer's disease One).

That is, the above results do not indicate that the exercise performance was deteriorated by the administration of the drug, and that the extracts of Gilson root did not affect the amount of gait activity.

Experimental Example  2: Y Maze type  Test (Y-maze test)

We conducted a Y - maze test to evaluate the temporal spatial perception of short - term memory.

The instrument used for this test consists of three arms, each of which has a length of 42 cm, a width of 3 cm, a height of 12 cm, and an angle of contact between the three arms is 120 °.

All experimental apparatus consisted of black polyvinyl plastic. Each branch was set as A, B, C, and the mouse was placed on one branch and allowed to move freely for 8 minutes.

It was recorded more than once only when the tail was completely inserted. (ABC, CAB, BCA; actual change, actual alternation) were assigned to each of three different branches. The alternation behavior is defined as sequentially entering all three, and is calculated by the following equation.

Change action power ( % ) = Actual change ( actualalternation ) / Maximum alternation x 100

(Highest change: total number of entries - 2)

As a result, amyloid beta peptide was directly injected into the brain (1.2 μg / mouse, i.c.v), and the alteration activity of the negative control group in which the nerve injury was induced was significantly decreased (p <0.05).

On the other hand, the spontaneous alternation of Gilson root extract group was significantly increased compared to the negative control group (P <0.05). An increase in spontaneous alternation suggests recovery of learning and memory (Fig. 2).

On the other hand, since the total entry indicating the total number of times to enter each zone has not changed, it is interpreted that the spontaneous alteration is not caused by the change in activity of the mouse.

Experimental Example  3: Morris water maze test

Through the passive avoidance test widely used as a method for measuring spatial learning and memory of rodents, the protective effect of gill root extract on neurons was confirmed.

The experiment was applied to the existing Morris method. One hour before the experiment, the mice were placed in an observation room and stabilized.

The specification of maze is 90cm in diameter and 32.5cm in height, and the diameter of the platform is 5cm. The perimeter of the underwater maze kept constant clues such as computer systems connected to video cameras and water temperature control devices. The maze was filled with water and placed below 1 cm above the water level so that the mouse could not see the platform. Maze was divided into four NEs, NWs, SEs and SWs using four markers, and a platform was installed in a quadrant of maze.

The Morris Underwater Maze test was conducted for 6 days. On the first day, the mouse was allowed to swim freely in the maze for 1 minute to adapt to the water, and the platform was not installed.

From the second day to the fifth day, the mice were allowed to swim four times a day for 10 minutes at the maze for 1 minute.

From the second day, one experiment for four days has already been completed for 10 seconds within 1 minute on the platform installed in maze, and the mouse has not been reached within 1 minute, or the platform has not been raised for 10 seconds. The experiment was terminated after placing it on the platform for 10 seconds. At this time, the position of the platform was fixed at the same position. On the 6th day, the platform was removed from the maze and the time spent on the mouse in the platform where the platform was located was measured (Fig. 3).

In order to perform the memory test on the last day of the Morris water maze learning, the platform was removed and a free swim was performed for 60 seconds. Through the Smart program, the time to stay in the quadrant of the platform during the total time was% Respectively.

The escape latency before the injection of amyloid beta peptide in the experimental group and control gradually decreased with time.

On the other hand, the escape latency of the negative control group treated with distilled water increased significantly after injection of amyloid beta peptide, while the escape latency of the control group administered with the Gil root extract was not significantly increased and remained at the same level as before.

These results suggest that the extracts of Gil root extract significantly inhibit neuronal apoptosis by amyloid-peptides and have excellent neuroprotective ability and can effectively alleviate or ameliorate neurodegenerative diseases.

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 (5)

Valeriana fauriei Briquet ) as an active ingredient for the prevention or treatment of degenerative brain diseases. The method according to claim 1,
The herbal extract is extracted with water, C1 to C4 lower alcohol, or a mixed solvent thereof. The method according to claim 1,
The degenerative brain disease may be selected from the group consisting of dementia, Alzheimer's disease, stroke, cerebral infarct, head trauma, cerebral arteriosclerosis, and Parkinson's disease. Lt; RTI ID = 0.0 &gt; of: &lt; / RTI &gt; Valeriana fauriei Briquet ) extract as an active ingredient for the prevention or amelioration of degenerative brain diseases. Valeriana fauriei Briquet ) extract as an active ingredient.

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