KR20180094566A - Composition comprising the extract of Belamcanda chinensis for preventing or treating neuro degenerative disease - Google Patents

Abstract

The present invention relates to a composition for preventing or treating degenerative brain diseases, containing a belamcanda chinensis extract as an active ingredient. The belamcanda chinensis extract of the present invention has shown excellent effects of improving memory in a passive avoidance experiment and a Morris water maze test using an animal model with reduced cognitive ability. Thus, the belamcanda extract can be used as a functional health food as well as a pharmaceutical composition for preventing and treating degenerative diseases while improving memory.

Description

[0001] The present invention relates to a composition for prevention or treatment of degenerative brain diseases,

The present invention relates to a composition for preventing or treating a degenerative brain disease, which comprises an extract of Leucineus as an active ingredient.

As the level of living improves and the life span of human beings increases, interest in various diseases related to aging and aging is increasing. In particular, degenerative brain diseases of the central nervous system such as Alzheimer's syndrome, Parkinson's syndrome and Huntington's syndrome become major social problems .

In particular, among the degenerative brain diseases, dementia is defined as a symptom complex that affects both mental cognitive function and social action ability, resulting in normal daily life disability. Recently, as the aging has progressed rapidly, It is emerging as a serious social and economic health issue for the elderly. Alzheimer's disease, cognitive dysfunction, vascular dementia due to cerebrovascular disease such as repeated cerebral infarction, and dementia due to other diseases are categorized as dementia, 50-60% of all dementia patients are known to be caused by Alzheimer's disease. In general, patients with Alzheimer 's disease exhibit clinically significant impairment in intellectual ability, emotional and behavioral changes, and then show signs of serious cerebral cortical dysfunction such as loss of directional sensation, memory impairment, and aphasia.

Cerebral vascular dementia is a major cause of atherosclerotic infarction and can be improved by treatment with thrombolytic agents. However, Alzheimer's disease rarely develops symptoms before the age of 50, but the tendency of the prevalence increases with age. , Which is a typical degenerative brain disease that is worsened as brain cells are gradually destroyed. The final diagnosis of this disease is only possible by pathologic examination through post-mortem examination, and is characterized by general atrophy of the cerebrum and nerve cell death at autopsy. Although many researchers have been actively studying the cause, the cause of the disease has not yet been fully elucidated.

In addition, the primary symptom of dementia disease, memory and cognitive decline, is known to be closely related to the cholinergic nervous system, and reports have shown that scopolamine, an antagonist of muscarinic receptors in postsynapse, (scopolamine) inhibits the binding of acetylcholine, a neurotransmitter liberated in presynapse, to muscarinic receptors, thereby temporarily interrupting the transmission of information, thereby damaging learning and memory, And is commonly used in memory-impaired animal models to be verified.

Currently, reversible AChE inhibitors, such as donepezil, galantamine, rivastigmine and tacrine, are used as therapeutic agents for Alzheimer's disease, but these drugs are only effective in the treatment of moderate symptom relief There are side effects such as nausea, diarrhea, vomiting, anorexia, abdominal pain and muscular contractions associated with peripheral cholinergic effects on the gastrointestinal tract. Especially, tacrine causes hepatotoxicity, have.

Therefore, it is necessary to develop new therapeutic agents that can treat degenerative brain diseases such as forgetfulness and memory improvement safely and effectively.

1. Korean Patent Publication No. 2010-0082044

It is an object of the present invention to provide a pharmaceutical composition for the prevention or treatment of degenerative brain diseases containing an extract of Zygomycetes as an active ingredient.

Another object of the present invention is to provide a health-functional food for improving or preventing degenerative brain diseases, which comprises an extract of Zygomycetes as an active ingredient.

In order to achieve the object of the present invention, the present invention provides a pharmaceutical composition for preventing or treating degenerative brain diseases containing an extract of Trichoderma as an active ingredient.

In one embodiment of the invention, the extract is selected from the group consisting of water, C1-C4 alcohol, hexane, ethyl acetate, butylene glycol, propylene glycol, glycerin, acetic acid, ether, chloroform, Lt; / RTI > may be obtained using a solvent of choice.

In one embodiment of the present invention, the solvent may be ethanol.

In one embodiment of the present invention, the degenerative brain disease is selected from the group consisting of Alzheimer's disease, dementia, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease, Disease, amnesia, learning disorder, and memory disorder.

In addition, the present invention provides a health functional food for improving or preventing degenerative brain diseases containing an extract of Zygomycetes as an active ingredient.

In one embodiment of the invention, the extract is selected from the group consisting of water, C1-C4 alcohol, hexane, ethyl acetate, butylene glycol, propylene glycol, glycerin, acetic acid, ether, chloroform, Lt; / RTI > may be obtained using a solvent of choice.

In one embodiment of the present invention, the solvent may be ethanol.

In one embodiment of the present invention, the degenerative brain disease is selected from the group consisting of Alzheimer's disease, dementia, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease, Disease, amnesia, learning disorder, and memory disorder.

The present invention relates to a composition for preventing or treating a degenerative brain disease comprising an extract of Zygomycetes as an active ingredient, wherein the Zygomycota extract of the present invention has excellent memory It is possible to use the extract as a health functional food as well as a pharmaceutical composition for improving memory and treating and preventing degenerative diseases.

Fig. 1 shows the result of measurement by the Y maze experiment that the extract of Belamcanda chinensis according to the present invention has an effect of improving memory. DNPZ is the group receiving donepezil.
FIG. 2 is a graph showing the results of the passive avoidance experiment conducted on the mice administered with the extract of the present invention, and the analysis of the degree of waiting time according to the treatment concentration of the extract of the leaves.
FIG. 3 is a graph showing the results of analyzing the degree of avoidance potential according to the treatment concentration of the extract obtained from Morris water maze.
FIG. 4 is an analysis of the memory enhancing effect of the extract obtained from the Morris water maze experiment, and shows the result of measuring the swimming time underwater according to the treatment concentration of the water extract.

The present invention is characterized by providing a pharmaceutical composition for preventing or treating a degenerative brain disease containing an extract of Leucineus as an active ingredient.

Belamcanda chinensis is a medicinal plant and has been used for a long time in combination with other medicines for various diseases of humans. Especially, it is known about anti-inflammatory action, antiallergic action and female hormone receptor binding action. However, The association with the disease has not yet been reported.

In this regard, it has been confirmed from the above that the extract of Cassia officinalis can be used as a new therapeutic agent for degenerative brain diseases. According to one embodiment of the present invention, the group administered with cassia extract to scopolamine- In the Y-maze test and the underwater maze test, the results showed that the memory performance was improved.

Accordingly, the present invention can be used as an active ingredient of a pharmaceutical composition capable of preventing or treating degenerative brain diseases.

The extract of the present invention may be obtained by isolating and extracting the extract from a human using an extracting and separating method known in the art. The 'extract' defined in the present invention may be prepared by using an appropriate solvent, . Any suitable solvent that can be used to obtain the extract may be any of those accepted in the art, and water or an organic solvent may be used. Examples of the solvent include alcohols having 1 to 4 carbon atoms, acetone, ether, and the like, including purified water, methanol, ethanol, propanol, isopropanol, butanol, Various solvents such as benzene, chloroform, ethyl acetate, methylene chloride, hexane and cyclohexane may be used alone or in combination. But is not limited to.

As the extraction method, any one of the methods such as hot water extraction method, cold extraction method, reflux cooling extraction method, solvent extraction method, steam distillation method, ultrasonic extraction method, elution method and compression method can be selected and used. In addition, the desired extract may be further subjected to a conventional fractionation process or may be purified using a conventional purification method. There is no limitation on the method for producing the extract of the present invention, and any known method can be used.

Preferably, ethanol is used as a solvent.

In particular, in comparison with the ethanol extract of the extracts obtained by using other solvents such as methanol and ethyl acetate extracts for the improvement of memory effect and the treatment effect of degenerative brain disease according to the present invention, Ethanol extracts significantly improved the memory effect.

In addition, the pharmaceutical composition of the present invention may be prepared by using pharmaceutically acceptable and physiologically acceptable adjuvants in addition to the above-mentioned effective ingredients. Examples of the adjuvants include excipients, disintegrants, sweeteners, binders, , A lubricant, a lubricant or a flavoring agent.

The pharmaceutical composition may be formulated into a pharmaceutical composition containing at least one pharmaceutically acceptable carrier in addition to the above-described active ingredients for administration.

The pharmaceutical composition may be in the form of granules, powders, tablets, coated tablets, capsules, suppositories, liquids, syrups, juices, suspensions, emulsions, drops or injectable solutions. For example, for formulation into tablets or capsules, the active ingredient may be combined with an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. Also, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included as a mixture. Suitable binders include, but are not limited to, natural sugars such as starch, gelatin, glucose or beta-lactose, natural and synthetic gums such as corn sweeteners, acacia, tracker candles or sodium oleate, sodium stearate, magnesium stearate, sodium Benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum and the like. Acceptable pharmaceutical carriers for compositions that are formulated into a liquid solution include sterile solutions suitable for the living body such as saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, One or more of these components may be mixed and used. If necessary, other conventional additives such as an antioxidant, a buffer, and a bacteriostatic agent may be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate into injectable solutions, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like. Further, it can be suitably formulated according to each disease or ingredient, using the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA as an appropriate method in the field.

In one embodiment of the present invention, the extract of the present invention may be contained in an amount of 0.1 to 50% by weight based on the total weight of the composition, and the composition may contain 50 to 200 mg Lt; / RTI >

The degenerative brain diseases that can be treated, prevented or ameliorated by the instant extract of the present invention include, but are not limited to, Alzheimer's disease, dementia, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, ) Disease, Creutzfeldt-Jakob disease, amnesia, learning and memory impairment.

Furthermore, the extract of the present invention can be used as a food composition for the improvement or prevention of degenerative brain diseases. In addition to containing an effective ingredient, mushroom extract, the food composition may contain various flavors or natural Carbohydrates and the like as additional components.

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 polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. The above-described flavors can be advantageously used as natural flavorings (tau martin), stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.).

The food composition of the present invention can be formulated in the same manner as the above pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, meat, chocolates, foods, confectionery, pizza, ram noodles, other noodles, gums, candy, ice cream, alcoholic beverages, vitamin complexes, .

In addition, the food composition may contain various additives such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and flavors such as natural flavorings, coloring agents and aging agents (cheese, chocolate, etc.), pectic acid and its salts , Alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks and the like. In addition, the food composition of the present invention may contain natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks.

The extract of the present invention, which is an effective ingredient of the present invention, is a natural substance and has little toxicity and side effects, so that it can be safely used even when taken for a long time.

The health functional food of the present invention can be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, and rings for the purpose of improving and preventing degenerative brain diseases.

In the present invention, the term " health functional food " refers to foods manufactured and processed using raw materials or ingredients having useful functions in accordance with Law No. 6727 on Health Functional Foods. Or to obtain a beneficial effect in health use such as physiological action.

The health functional foods of the present invention may contain conventional food additives and, unless otherwise specified, whether or not they are suitable as food additives are classified according to the General Rules for Food Additives approved by the Food and Drug Administration, Standards and standards.

Examples of the items listed in the above-mentioned "food additives" include chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; Natural additives such as persimmon extract, licorice extract, crystalline cellulose, high color pigment and guar gum; L-glutamic acid sodium preparations, noodle-added alkalis, preservative preparations, tar coloring preparations and the like.

For example, the health functional food in the form of tablets may be prepared by granulating a mixture obtained by mixing the extract of the present invention, which is an effective ingredient of the present invention, with an excipient, a binder, a disintegrant and other additives in a usual manner, Alternatively, the mixture can be directly compression molded. In addition, the health functional food of the tablet form may contain a mating agent or the like if necessary.

The hard capsule of the capsule type health functional food can be prepared by filling a normal hard capsule with a mixture of the extract of the present invention, which is an effective ingredient of the present invention, with an additive such as an excipient. The soft capsule can be prepared by adding a mushroom extract to an additive such as an excipient And filling the mixture with 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 ring-shaped health functional food can be prepared by molding a mixture of a mushroom extract, an active ingredient of the present invention, an excipient, a binder, a disintegrant, and the like by a conventionally known method and, if necessary, Or the surface may be coated with a material such as starch, talc.

The granular form of the health functional food may be prepared by granulating the mixture of the extract of the present invention and the excipient, binder, disintegrant, etc. as the active ingredient of the present invention into a granule by a known method, and if necessary, ≪ / RTI >

The health functional food may be in the form of tablets, capsules, pills or liquids, and examples thereof include beverages, meat, chocolates, foods, confectionery, pizza, ramen, other noodles, gums, candy, ice cream, alcoholic beverages, And health supplement foods.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these examples are for illustrative purposes only and that the scope of the present invention is not construed as being limited by these examples.

≪ Example 1 >

Preparation of extract

Belamcanda chinensis Leman) was purchased from Guilin Pharmaceutical Co. (Daegu). The extracts were prepared by adding 70% ethanol in an amount corresponding to 10 times the weight of the raw material, and then extracting the mixture by ultrasonic irradiation three times. The extracts were concentrated under reduced pressure to obtain a crude extract, Dried and used in the following experiments. The yield was 42.39%.

≪ Example 2 >

The effect of extracts on the growth of memory

In order to confirm whether the extract of the present invention has memory enhancing effect, animal experiments were conducted. The animals for the experiment were 4-week-old male ICR mice supplied from Daehan BioLink (Chungbuk, Korea). The darkness was maintained at a temperature of 23 ± 2 ℃ and humidity of 50 ± 10%. The bred mice were administered with the extracts of mushrooms in the following manner. First, the extracts were dissolved in 0.9% saline solution and administered orally to mice at 1, 50, 100 and 200 mg / kg dose 1 hour before the start of the experiment. The control group was orally administered only the 0.9% saline solution in the same volume as the control group. As a positive control, 5 mg / kg of donepezil, a treatment for dementia, was dissolved in 0.9% saline solution and orally administered to mice 1 hour before the experiment. In addition, scopolamine, a parasympathetic inhibitor, was dissolved in 0.9% saline solution and administered to all experimental groups except for the control group by intraperitoneal administration 30 minutes before the experiment.

As described above, the Y-maze test was performed to test the memory test. The Y-maze test is a method for measuring short-term memory and is a method for evaluating the ability to act sequentially. The measuring equipment is composed of black polyvinyl plastic and consists of three branches. The length of each branch is 40 cm, width is 6.8 cm, height is 15.5 cm, and the angle of the three branches is 120 °. The experimental animals were added to each branch for 8 minutes, and the number of times the animals entered the branch until the tail of the animal and the number of turns in each branch were given 1 point (actual change).

The alternation behavior is defined as entering all three without overlap, and is calculated by the following equation:

Change Actual Power (%) = actual alternation / maximum alternation × 100 (highest change: total number of entries - 2)

As a result of analyzing the effect of suppressing the memory impairment of memory loss due to scopolamine in the experimental mouse group to which the extract of the present invention was administered, , And spontaneous alterations (%) were significantly decreased in patients with memory impairment due to scopolamine administration. In contrast, the number of spontaneous alterations Respectively.

≪ Example 3 >

Passive avoidance experiment

Passive avoidance test was used to examine the effect of scopolamine on memory retention and to improve the memory performance of experimental animals. For this purpose, the passive evasive box was 42.5cm long and 35.5cm long. It was divided into a dark room and a bright room. When a laboratory animal was placed in a bright room, the room was moved to a dark room. On the day following the electric shock, when the test animals were placed back in a bright room, the electrical impulses in the dark room remained and remained in the bright room. The memory was assessed by measuring the step-through latency.

The results showed that the latency time of the scopolamine-treated group was significantly lower than that of the control group in the scopolamine-treated group, and that of the scopolamine-treated group was significantly decreased at 200, 100 and 50 mg / kg The latency time was significantly increased in a dose-dependent manner in a single oral dose group (see FIG. 2).

Therefore, the inventors of the present invention have found that the instant extract of the present invention can effectively enhance memory.

< Example  4>

Morris Underwater maze  Experiment

Passive avoidance test was performed to confirm the memory improvement and enhancement effect of the experimental animals in the memory declining animal group and the cyanobacterium extract group administered with scopolamine. The experiment was performed using an animal cognitive ability measuring device (EthoVision Maze test system, Noldus Information Technology, Wageningen, Netherlands), and four markers were placed around a cylindrical water tank with a diameter of 90 cm, a height of 45 cm, and a surface height of 61.5 cm We remembered this and measured the escape latency, which is the time taken to visit the platform, when we visited the platform installed at any place in the tank and stayed for more than 5 seconds. Experiments were conducted on 4 occasions, 4 times a day, four times a day, and the mean value was defined as mean escape latency. If the animal can not find the platform within 60 seconds, the animal is allowed to memorize the platform for 15 seconds. On the last day, the platform was removed and the animals were allowed to swim for 120 seconds. The swimming time was measured in the area where the platform was placed and the memory was compared.

As a result of the analysis, as shown in Figs. 3 and 4, in the group treated with the extracts of 200, 100, and 50 mg / kg, the escape latency time was remarkably decreased on the third day of the experiment And the dose of quercetin was significantly decreased in the order of 200, 100 and 50 mg / kg on the last day of the experiment.

Therefore, the inventors of the present invention have concluded that the extract of the present invention can be used as a new therapeutic agent for the treatment of degenerative brain diseases such as amelioration and memory improvement based on these results.

The present invention has been described with reference to the preferred embodiments. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the present invention is defined by the appended claims rather than by the foregoing description, and all differences within the scope of equivalents thereof should be construed as being included in the present invention.

Claims (9)

A pharmaceutical composition for the prevention or treatment of a degenerative brain disease comprising an extract of a human body as an active ingredient. The method according to claim 1,
The extract is obtained by using a solvent selected from the group consisting of water, C1 to C4 alcohol, hexane, ethyl acetate, butylene glycol, propylene glycol, glycerin, acetic acid, ether, chloroform and a mixed solvent thereof &Lt; / RTI &gt; 3. The method of claim 2,
Wherein the solvent is ethanol. The method according to claim 1,
The degenerative brain disease is selected from the group consisting of Alzheimer's disease, dementia, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease, forgetfulness, Lt; RTI ID = 0.0 &gt; 1, &lt; / RTI &gt; The method according to claim 1,
Wherein the composition can be administered in an amount of 50 to 200 mg based on the individual weight (kg). A health functional food for improving or preventing a degenerative brain disease containing an extract of Mushroom as an active ingredient. The method according to claim 6,
The extract is obtained by using a solvent selected from the group consisting of water, C1 to C4 alcohol, hexane, ethyl acetate, butylene glycol, propylene glycol, glycerin, acetic acid, ether, chloroform and a mixed solvent thereof Health functional food characterized by. The method according to claim 6,
Wherein the solvent is ethanol. The method according to claim 6,
The degenerative brain disease is selected from the group consisting of Alzheimer's disease, dementia, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease, forgetfulness, Or a pharmaceutically acceptable salt thereof.

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