KR20150138976A - Composition containing dehydroglyasperin C for preventing or treating cognitive dysfunction - Google Patents

Abstract

The present invention relates to a composition containing dehydroglyasperin C as an active ingredient for preventing or treating cognitive function disorders. The dehydroglyasperin C of the present invention can be helpfully used in preventing or treating memory and cognitive function disorders due to having excellent effects in improving cognitive function and memory.

Description

[0001] The present invention relates to a composition for preventing or treating a cognitive dysfunction containing dehydrogliasperin C as an active ingredient,

The present invention relates to a composition for preventing or treating cognitive dysfunction which contains dehydroglial asperin C as an active ingredient.

With advances in medical technology and improved living standards, the average life expectancy of human beings has doubled over the last half-century, resulting in a rapid increase in the proportion of the elderly population to the total population. Accordingly, there is a growing demand for the development of functional materials and foods capable of preventing and treating cognitive dysfunction, including dementia.

Degenerative brain diseases are characterized by disorders of cognitive function, such as memory loss, and include various diseases such as dementia, Parkinson's disease, stroke and Huntington's disease. Dementia, a typical degenerative brain disease, is a brain disorder characterized by general cognitive impairment, usually caused by chronic or progressive brain disease, and impairs many of the higher levels of cerebral function, including memory, thinking, comprehension, comprehension, learning and verbalisation. The exact cause of such dementia has not yet been elucidated, and presumptive causes are cholinergic neuronal damage of the cerebral basal ganglia, reduction of neurotransmitters, and accumulation of beta-amyloid protein And oxidative stress have been reported (Davies P. et al., Lancet, 21, 1403, 1976. Rocher, AE et al., J. Biol. Chem., 273, 29719, 1988. Coyle, JT et al. : Science, 262, 689, 1993).

In particular, it is known that the incidence of dementia in elderly people is significantly higher than that of elderly people aged 75-84, which is about 20%, and about 50% As a matter of course. As a result of this, the economic loss is so great that the social cost of treatment for dementia in Korea is estimated to be 3.4 trillion to 4.40 trillion won, Source). In the United States, the cost of treatment for dementia is estimated to be between $ 1000 and $ 120 billion annually. Therefore, as society becomes more aging, senile dementia is emerging as the greatest health problem to be solved by humanity in the 21st century. It is also a cultural issue that pursues an attitude of living with a healthy life and spiritual leisure, BACKGROUND ART [0002] There is a growing demand for functional materials that can prevent dementia due to the necessity of the era requiring various well-being products to be released.

Accordingly, many studies have been conducted to develop drugs and functional foods for the treatment of dementia, and as a result, the activity of acetylcholinesterase, an enzyme that degrades acetylcholine, a neurotransmitter, has been inhibited Acetylcholinesterase inhibitors that increase acetylcholine in the brain have been developed and marketed. Representative drugs include FDA-approved drugs tacrine, donepezil, COGNEX, Galantamine, and Rivastigmine (Desai, AK et al. Neurology, 64: 34-39 (2005)). However, these acetylcholinesterase inhibitors are effective only when the cholinergic nerve is not functionally impaired, and are only effective in the early stages of mild or severe senile dementia, as they decline with declining cholinergic function. Most of these inhibitors are very expensive, exhibit cholinergic side effects of peripheral nerves, have a short half-life, and have the disadvantage of causing serious adverse effects such as liver toxicity, vomiting and loss of appetite (Christie, JE et al., Br. Psychiatry, 138: 46-50 (1981)). Particularly, 9-amino-1,2,3,4-tetrahydroacridine (THA), an active ingredient of Cognex, shows improvement in perception ability when administered orally (Summers, WK, et al., New Engl J Med, 315: 1241-1246 (1986)), severe side effects such as tremor, dizziness, liver toxicity, and so on. In addition, tacrine appears to be hepatotoxic in about half of the treated patients. Donepezil causes gastrointestinal disorders such as nausea, vomiting, diarrhea and constipation, and galantamine causes side effects such as nausea and vomiting, making it difficult to use for a long period of time.

Therefore, in order to prevent and improve degenerative brain diseases, it is required to develop new cognitive function-improving substances that delay brain cell destruction and aging to protect brain cells, restore cognitive function, and promote regeneration of brain cells .

The present inventors have been studying natural products and compounds separated therefrom in order to develop a drug having an excellent effect of preventing or treating cognitive dysfunction, and it has been found that dehydroglial perine C is excellent in improving cognitive ability and memory And completed the present invention.

It is an object of the present invention to provide a composition for preventing or treating cognitive dysfunction which contains dehydroglial asperin C as an active ingredient.

In order to accomplish the above object, the present invention provides a pharmaceutical composition for preventing or treating cognitive dysfunction comprising dehydroglial asperin C as an active ingredient.

The present invention also provides a food composition for preventing or ameliorating a cognitive dysfunction which contains dehydroglial asperin C as an active ingredient.

The dehydroglia superine C of the present invention is excellent in improving cognitive ability and memory, and thus can be effectively used for the prevention or treatment of memory and cognitive dysfunction.

Brief Description of the Drawings Fig. 1 is a diagram showing the effect of acetylcholinesterase inhibition of dehydroglial asperin C; Fig.
FIG. 2 is a diagram showing the effect of improving the behavioral ability of dehydroglial perine.
3 is a graph showing an effect of improving the passive evasion ability of dehydroglial plusin C;
4 is a graph showing the results of a Morris water maze experiment performed to measure the cognitive function and memory effect of dehydroglial perine C;

The present invention provides a composition for the prevention or treatment of cognitive dysfunction which contains dehydroglial plusin C as an active ingredient.

The composition comprises a pharmaceutical composition and a food composition.

The active ingredient dehydroglial perine C of the present invention can be obtained from licorice by a conventional extraction method.

The dehydrogliasperrin C of the present invention is excellent in improving cognitive ability and memory effect, and thus can be effectively used for preventing or treating cognitive dysfunction.

The cognitive dysfunction-related diseases are selected from the group consisting of Alzheimer's disease, vascular dementia, Diffuse lewy body dementia, Huntington's disease, pick disease, Kruszfeld- Creutzfeldt-Jakob disease, dementia due to head injury, or Parkinson ' s disease.

The composition of the present invention may contain one or more known active ingredients having an effect of preventing or treating cognitive dysfunction together with dehydrogliasperin C,

The compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions. In addition, it can be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, oral formulations such as syrups and aerosols, external preparations, suppositories and sterilized injection solutions according to a conventional method. Suitable formulations known in the art are preferably those as disclosed in Remington ' s Pharmaceutical Science, recently, Mack Publishing Company, Easton PA. Examples of carriers, excipients and diluents which may be included include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. When the composition is formulated, it is prepared using a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, or an excipient 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, lactose, Gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized 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 term "administering" as used herein is meant to provide any desired composition of the invention to a subject in any suitable manner.

The preferred dosage of the pharmaceutical composition of the present invention varies depending on the condition and the weight of the individual, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. For the desired effect, the dehydroglial asperin C of the present invention may be administered in an amount of 0.1 mg / kg to 50000 mg / kg per day, which may be administered once a day or divided into several doses.

The pharmaceutical composition of the present invention may be administered to a subject in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine dural or intracerebral injection.

The composition of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers for the prevention and treatment of cognitive dysfunction.

In the present invention, the term "health functional food" refers to a food having a biological control function such as prevention and improvement of disease, bio-defense, immunity, recovery after disease and aging inhibition.

The composition of the present invention may be added to a health functional food for the purpose of preventing or improving cognitive dysfunction. When the dehydroglial asperin C of the present invention is used as a food additive, the dehydroglial asperin C can be added as it is, or used together with other food or food ingredients, and can be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment). Generally, the dehydrogliasperrin C of the present invention is added in an amount of not more than 15% by weight, preferably not more than 10% by weight based on the raw material, in the production of food or beverage. However, in the case of long-term intake for the purpose of health and hygiene or for the purpose of controlling health, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range.

There is no particular limitation on the kind of the food. Examples of the foods to which the above substances can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include health foods in a conventional sense.

The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. The natural carbohydrates may be monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, natural sweeteners such as dextrin and cyclodextrin, synthetic sweeteners such as saccharine and aspartame, and the like. The ratio of the natural carbohydrate is generally about 0.01 to 10 g, preferably about 0.01 to 0.1 g per 100 ml of the composition of the present invention.

In addition to the above, the composition of the present invention may further contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, A carbonating agent used in a carbonated beverage, and the like. In addition, the composition of the present invention may comprise flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. Although the ratio of such additives is not critical, it is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

Hereinafter, preferred examples, experimental examples, and formulation examples are provided to facilitate understanding of the present invention. However, the following examples, experimental examples and preparation examples are provided only for the purpose of easier understanding of the present invention, and thus the present invention is not limited thereto.

Experimental Example 1. Assessment of acetylcholinesterase (AChE) activity of dehydroglialaspirin C

In order to confirm the effect of improving the cognitive function of dehydroglia asperin C of the present invention, the activity of isethylcholinesterase (AChE) of dehydroglia asperin C was measured.

Specifically, the activity of acetylcholine esterase (AChE) was analyzed by modifying Ellman 's method using acetylcholine iodide as a substrate. Acetylcholinesterase (AChE) was prepared by dividing the cerebral cortex and hippocampus of mice and adding 10 times phosphate buffer solution (12.5 mM phosphate buffer solution containing 400 mM NaCl, pH 7.0) and pulverizing using sonication The homogenate was centrifuged at 1000 xg for 4 minutes at 4, and the supernatant was used as a sample of acetylcholinesterase (AChE). 5 L of the target substance, 640 L of buffer solution, 100 L of buffer solution (100 mM, sodium phosphate buffer, pH 8.0) diluted to a concentration of 1 mg / mL per each concentration of dehydroglial perine C And 25 L of a solution consisting of an enzyme source of Ellman's reagent (Ellman's reagent: 10 mM DTNB (5,5'-dithiobis-bis (2-nitrobenzoic acid)) and 15 mM NaHCO3 were mixed and reacted at 25 for 30 minutes. After the addition of 10 L of 75 mM acetylthiocholine iodide solution to the solution, the absorbance was measured at 415 nm after the addition of acetylcholine iodide instead of acetylcholine iodide as a control. (AChE) activity of the reaction solution to which each substance was added when the activity of acetylcholinesterase (AChE) of the control group was taken as 100%, and that the activity of the acetylcholinesteraseIt was confirmed to be. The results are shown in Figure 1;

As shown in FIG. 1, when acetolcholinesterase activity test was conducted, it was confirmed that dehydroglial perine C inhibited acetylcholinesterase (AChE) in a concentration-dependent manner when the cerebral cortex was used as an enzyme source .

Experimental Example 2: Test of ability to change behavior (Y-maze test)

In order to confirm the effect of improving the cognitive function of dehydroglial perine C of the present invention, a behavior modification ability test (Y-maze test) was performed using a scopolamine-induced forgetting rat.

Specifically, mice were given sporocolamine to induce amnesia, and mice receiving amnesia were treated with dehydrogliasperin C. Y-maze (It has three Y-shaped arms. The material of the instrument is made of polyvinyl plastic. It has length × height × width 42 × 3 × 12 cm, ) Were set as A, B and C, and mice were carefully placed on one branch and allowed to move freely for 8 minutes. Then, the branches containing the mice were recorded. At this time, we counted only when the tail had completely entered, and gave 1 point (actual alteration) when it entered three different branches in turn. The behavior change ability was calculated by the following equation.

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

The results are shown in Fig.

As shown in Fig. 2, it was confirmed that dehydroglial perine C improves concentration-dependent ability to change behavior reduced by treatment with scopolamine.

Experimental Example 3. Passive avoidance experiment

In order to confirm the effect of improving the cognitive function of dehydroglial perine C of the present invention, a passive avoidance experiment was conducted.

Specifically, the Gemini avoidance system (San Diego Instruments, San Diego, USA) is divided into two rooms of the same size in the size of a shuttle box (52.6 x 17.3 x 21.3 cm) Is equipped with a guillotine door (8.9 x 8.9 cm) that can be opened and closed automatically up and down. In the right room, a very bright light bulb was installed to create a bright environment in which the animals were disliked. In the left room, light was prevented from entering, and the experimental animals were relatively comfortable.

The right chamber of the reciprocating box was turned on, and the head of the experimental animal was gently lowered toward the side of the guillotine door. The experimental animals were searched for 10 seconds, and the guillotine door was opened to enter the dark compartment. Experimental animals navigated the room instinctively to the dark left chamber, which excluded mice that did not enter the dark within 300 seconds of opening the guillotine door. Once the mouse entered the dark side, the guillotine door was closed and a 0.5 mA electric shock was allowed to flow through the grid floor for 3 seconds.

After 24 hours from the end of the experiment, the experimental animal used in the experiment was placed in a round trip box, and after searching for 10 seconds, the latency time (retention time) Was measured up to 300 seconds. The results are shown in Fig.

As shown in Fig. 3, the retention time was shortened in the group in which scopolamine was induced compared to the normal group, and the group administered with dehydroglial asparagine C at 5 to 20 mg / kg bw was dose-dependent And the retention time of the experimental animals was prolonged.

Experimental Example 4. Morris Underwater Maze Test

The Morris Underwater Labyrinth test can be used to measure spatial learning and cognitive enhancement, and is often used as a method to explore drugs for the prevention or treatment of dementia. The water tank used as an underwater maze was a circular cylinder with a diameter of 90 cm and a height of 45 cm, and water having a temperature of 25 ± 2 ° C was filled to a height of 30 cm for the experiment. The perimeter of the underwater maze consisted of various shapes of space clues hanging on the video camera, the experimental table, and the water tank wall. The escapement was 6 cm in diameter, and an escape rod was installed 1 cm above the water height so that the mouse could see the escape platform. We divide the water maze into four quadrants and divide it into NE, NW, SE and SW, install a refuge in one quadrant, Respectively. The Morris Underwater Maze test was conducted for 6 days. On the first day, each mouse is allowed to swim freely in the maze for 1 minute so that it can adapt to the water. At this time, the platform is not installed, and each mouse is given 4 times a day for 1 minute from day 2 to day 5 We were allowed to swim at maze every 30 seconds. One test for 4 days starting from the second day is a mouse that has been already on the platform installed in maze for 10 seconds within 1 minute and the mouse not reaching the platform within 1 minute or the platform for 10 seconds after the experiment After the experiment, the platform was artificially put on the platform for 10 seconds and the experiment was terminated. At this time, the platform was fixed at the same position. On the sixth day, the platform was removed from the maze and the time the mouse stopped at the platform was measured. Scopolamine was used as an amenorrheic agent, and injections were peritoneally administered at 1 mg / kg body weight 30 minutes before the first intake on a daily basis. The results are shown in Fig.

As shown in FIG. 4, the mice in the group administered with dehydroglial plus neuron C showed improved cognitive ability and memory compared to the control group, and the time spent in the escape zone was significantly increased.

Therefore, the dehydroglial asperin C of the present invention is excellent in improving the cognitive ability and memory, and can be effectively used for preventing or treating cognitive dysfunction.

Hereinafter, a pharmaceutical composition for preventing or treating cognitive dysfunction and a food composition for preventing or ameliorating a cognitive dysfunction containing dehydrogliasperin C according to the present invention will be described. However, the present invention is not limited thereto But rather just to explain it specifically.

Formulation Example 1. Preparation of pharmaceutical preparations

1. Manufacturing of powder

Dehydrogliaferrin C 20 mg

Lactose 100 mg

Talc 10 mg

The above components are mixed and filled in airtight bags to prepare powders.

2. Preparation of tablets

Dehydrogliaferrin C 10 mg

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

3. Preparation of capsules

Dehydrogliaferrin C 10 mg

Crystalline cellulose 3 mg

Lactose 14.8 mg

Magnesium stearate 0.2 mg

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

4. Preparation of injections

Dehydrogliaferrin C 10 mg

180 mg mannitol

Sterile sterilized water for injection 2974 mg

Na ₂ HPO ₄ 2H ₂ O 26 mg

(2 ml) per 1 ampoule in accordance with the usual injection preparation method.

5. Manufacture of liquids

Dehydrogliaferrin C 20 mg

10 g per isomer

5 g mannitol

Purified water quantity

Each component was added and dissolved in purified water according to the usual liquid preparation method, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was added with purified water to adjust the total volume to 100 ml, And sterilized to prepare a liquid preparation.

Formulation Example 2. Preparation of food preparation

1. Manufacture of health food

Dehydrogliaferrin C 100 mg

Vitamin mixture quantity

70 g of vitamin A acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

0.15 mg of vitamin B2

Vitamin B6 0.5 mg

0.2 g of vitamin B12

Vitamin C 10 mg

Biotin 10 g

Nicotinic acid amide 1.7 mg

Folate 50 g

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

2. Manufacture of health drinks

Dehydrogliaferrin C 100 mg

Vitamin C 15 g

Vitamin E (powder) 100 g

19.75 g of ferrous lactate

3.5 g of zinc oxide

Nicotinic acid amide 3.5 g

Vitamin A 0.2 g

Vitamin B1 0.25 g

Vitamin B2 0.3g

Water quantification

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 DEG C for about 1 hour. The solution thus prepared was filtered and sterilized in a sterilized 2 liter container, It is used in the production of the health beverage composition of the invention.

Although the compositional ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the compounding ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.

Claims (2)

A pharmaceutical composition for preventing or treating cognitive dysfunction comprising dehydrogliasperin C as an active ingredient.
A food composition for preventing or ameliorating a cognitive dysfunction containing dehydroglial perine C as an active ingredient.

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