KR20150078372A - Composition containing Reseda luteola L. extract or its fraction for preventing or treating cognitive dysfunction - Google Patents

Abstract

The present invention relates to a composition comprising mignonette extracts or fractions as an active ingredient for preventing or treating a cognitive dysfunction. The mignonette extracts or fractions can be usefully used in preventing or treating a memory and cognitive dysfunction by having an excellent effect of improving cognitive ability and behavioral alteration ability.

Description

The present invention relates to a composition for preventing or treating cognitive dysfunction, which contains, as an active ingredient,

The present invention relates to a composition for preventing or treating a cognitive dysfunction comprising an extract or a fraction thereof as an active ingredient.

Many of the degenerative diseases of the elderly are causing social and economic problems due to the increase in the elderly population worldwide as well as in Korea. Degenerative brain disease is a disorder characterized by impaired cognitive function such as memory loss, and includes various diseases such as dementia, Parkinson's disease, stroke, and Huntington's disease. In addition, in modern society, the increase of degenerative brain diseases such as senile dementia due to the rapid increase of the elderly population is emerging as a serious social problem. However, until now, no effective preventive or therapeutic methods have been developed for the prevention and treatment of this disease It is true. Dementia, a typical degenerative brain disease, is a disorder characterized by general cognitive impairment, usually caused by chronic or progressive brain disease, and impairs a number of higher levels of cerebral function, including memory, thinking, comprehension, comprehension, learning and language judgment. The cause of dementia is not clearly known, but the presumed cause is damage to the cholinergic neurons of the cerebral basal ganglia, decrease of neurotransmitters, beta-amyloid protein accumulation by oxidative stress, Chemie, 273, p 29719, 1988. Coyle et al., Science, 262, p689, < RTI ID = 0.0 > 1993).

In this study, we investigated the effects of neurotransmitters on neurotransmitters in neurons (Zarow, C et al., Arch. Neurol, 60, pp 337-341, 2003) Indolamine, which is synthesized from catecholamine and tryptophan, is found in various body parts along with its metabolites. The concentration of this substance in neurons is a biochemical indicator of sympathetic function Can be used. In particular, the aging process and the concentration of amines and metabolites in the brain and the ability to act on receptors can be traced to diagnose the aging of the brain and related diseases. Measurement of glutamate or gamma aminobutyric acid (GABA) content in the brain is applied to the diagnosis of degenerative diseases or Alzheimer's disease in the brain. This is because excitatory amino acids (EAA), such as glutamate and aspartate, act as a major excitatory transmitter in the central nervous system, causing neuronal survival, synaptogenesis, learning and memory, neuronal plasticity (Bowen, DM et al., Brain, 99, pp 459-496, 1976). However, when they accumulate at a high concentration in the extracellular fluid, they represent a neurotoxin. In particular, glutamate is useful as a therapeutic agent for hypoglycemia, status epilepticus, ischemia, hypoxia, head trauma, (Masotto, C et al., Phamacol. Res. Commun., 17, pp. 749-772, 1985) have been reported to induce neuronal cell necrosis. In addition, brain glutamate and GABA have been reported to cause nervous system damage in association with brain degenerative diseases and Alzheimer's (Choi, D.W., J. Neurosci, 7, p369, 1987).

On the other hand, senile dementia, a disease in which cognitive ability gradually disappears, is also related to the activity of cholinergic neurons in the central nervous system, which is mainly caused by a marked decrease in the activities of acetylcholine and choline acetyltransferase in the brain It is known. At present more than 60 neurotransmitters have been found and acetylcholine, catecholamine, glutamate and GABA have been reported to play an important role in various aspects of learning and memory (Cummings JL et al., Neurology, 44, pp 2308-14, 1994).

Reseda luteola is a single year beginning in the Mediterranean and south-west Asia. As a herb plant from abroad, it is used as fragrance, essential oil raw material, sachet, potpourri, but it has not been commercialized in Korea. It grows up to 80cm in height and branches out well. Root foliage is rosetta type and upper part is spinning type. The flowers run on a lot of silkworms, and they have a good fragrance and are used as a source of fragrance and essential oils. They are used as sachets and potpourri.

In addition, the root of Neck Seed has been loved as a yellow dyeing raw material, and Neck Seed is used as a green color dye to the extent that Mignonette means green gray.

The inventors of the present invention studied the natural products and the compounds separated therefrom in order to develop a drug having an excellent effect of preventing or treating cognitive dysfunction. And completed the present invention.

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

In order to accomplish the above object, the present invention provides a pharmaceutical composition for preventing or treating cognitive dysfunction, which comprises an extract or a fractions thereof as an active ingredient.

In addition, the present invention provides a food composition for preventing or ameliorating a cognitive dysfunction, which comprises an extract or a fraction of Momordica sativa as an active ingredient.

The throat extract or fraction of the present invention has an excellent effect of improving cognitive ability and behavior change ability, and thus can be effectively used for preventing or treating memory and cognitive dysfunction.

FIG. 1 shows the effect of improving the behavior-modifying ability of the extract and fractions of Mulberry Seed extract in the Y-maze test.

The present invention provides a composition for the prevention or treatment of cognitive dysfunction comprising an extract or a fraction thereof as an active ingredient.

The composition comprises a pharmaceutical composition and a food composition.

Hereinafter, the present invention will be described in detail.

The effective ingredient of the present invention can be obtained by conventional extraction and fractionation methods.

In the present invention, it was obtained by the following method.

First, the neck seaweed is cleanly washed with water to remove foreign matter, and then dried and pulverized at room temperature. The ground neckwood powder is immersed in a water solvent and extracted overnight. The extraction solvent is not limited thereto, but at least one solvent selected from water, an alcohol having 1 to 4 carbon atoms, and a mixed solvent thereof may be used, and water is preferable. After filtering the neck seaweed extract, the solvent is evaporated and concentrated to give the final neck heather extract.

In addition, the Mokcheoncho extract prepared as described above is suspended in distilled water, placed in a separating funnel, and fractionated with an organic solvent to obtain a Mokcheoncho fraction. The organic solvent includes, but is not limited to, hexane, ethyl acetate, butanol, and preferably hexane.

The throat seed extract or fraction of the present invention is excellent in improving memory and cognitive ability, and thus can be effectively used for preventing or treating cognitive dysfunction.

In addition, the sorghum extract or fraction of the present invention has an effect of improving the behavior change ability.

The cognitive dysfunction-related diseases include Alzheimer ' s disease, cerebrovascular dementia, pick disease, Creutzfeldt-Jakob disease, dementia caused by head injury or Parkinson ' s disease But is not limited thereto.

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 a sesame extract or fraction thereof.

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

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 thymus extracts or fractions of the present invention may be administered in an amount of 1 mg / kg to 10000 mg / kg per day, or may be administered once a day or divided into several times.

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 thymus extract or fraction of the present invention is used as a food additive, the thymus extract or fraction may be added as it is or may be used together with other food or food ingredients, and may 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, in the production of a food or beverage, the neck-neck extract or fraction 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. 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 foods to which the above substances can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen and other 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 the present invention is not limited thereto.

Example 1: Preparation of a tree seedling extract

The neck seaweed was cleanly washed with water to remove foreign matter, and then dried and pulverized at room temperature. The ground wood meal powder was immersed in water and extracted overnight. After filtering the neck seaweed extract, the solvent was evaporated and concentrated to give the final neck heather extract.

Example 2: Preparation of a fungicide fraction

The water extract prepared in Example 1 was suspended in distilled water, placed in a separate funnel, and then washed with hexane, ethyl acetate (EtOAc), butanol (BuOH) and water (H ₂ O) Followed by sequential solvent fractionation. The same procedure was repeated three times to obtain a hexane fraction, an ethyl acetate fraction, a butanol fraction and a water-soluble fraction, respectively.

Experimental Example 1. Confirmation of acetylcholine esterase inhibitory effect of the herb extract

In order to confirm acetylcholine esterase (AChE) inhibitory effect of thymus extract, Ellman method using acetylcholine iodide as a substrate was modified and analyzed. 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, pH 7.0, containing 400 mM NaCl), sonication, and pulverized. g for 10 minutes at < RTI ID = 0.0 > 4 C. < / RTI > The supernatant was then obtained and the supernatant used as a sample of AChE. Each of the extracts prepared in Example 1 was diluted with phosphate buffer (100 mM, sodium phosphate buffer, pH 8.0) to a concentration of 1 mg / mL, and 5 μL of the diluted target substance, 640 μL of the buffer solution, 25 μL of a solution consisting of 100 μL of the enzyme source, buffered Ellman's reagent (10 mM DTNB (5-dithiobis-bis (2-nitrobenzoic acid)) and 15 mM NaHCO ₃ was mixed and reacted at 25 ° C. for 30 minutes Then, 10 μL of 75 mM iodide acetylcholine solution was added to this solution, and the absorbance was measured at 415 nm for 10 minutes, after which the absorbance was measured by adding saline instead of acetylcholine iodide as a control. At this time, it was confirmed that the nonspecific reaction between the extract and the reagent for enzyme activity measurement did not occur, and when the AChE activity of the control group was taken as 100%, the inhibition of AChE activity Was. Confirmation that the neck Seocho extract exhibited a high acetylcholinesterase inhibitory activity.

Experimental Example 2. Identification of the effect of improving the behavior modification ability in the forgetfulness model of the extract

The Y-maze test was conducted to confirm the effect of improving the behavior modification ability of the Seokseocho extract and fractions. Mice were administered scopolamine to induce amnesia, and then the neck and neck extracts and the hexane fractions prepared in Examples 1 and 2 were administered, respectively. The Y-maze has three Y-shaped arms, the material of which is made of poly-secret plastic, length × height × width 42 × 3 × 12cm and the angle of contact between the arms is 12 °. ) Were set as A, B, and C, and the mouse was carefully placed on one branch and allowed to move freely for 8 minutes. Then, the branch containing the mouse was 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, and the results are shown in FIG.

Behavior change ability (%) = actual alternation / maximum alternation × 100 (highest change: total number of entries -2)

As shown in Fig. 1, the extracts and fractions of the Fusarium oxysporum significantly improved the behavior modification ability reduced by scopolamine, and in particular, the hexane fraction from which luteolin was removed showed the ability to change the behavior of the mouse Respectively.

Hereinafter, a pharmaceutical composition for preventing or treating cognitive dysfunction containing the thymus extract or fraction of the present invention and a preparation example of a food composition for preventing or ameliorating cognitive dysfunction will be described, but the present invention is not limited thereto It is just a specific description.

Formulation Example 1. Preparation of pharmaceutical preparations

1. Manufacturing of powder

20 mg < RTI ID = 0.0 >

Lactose 100 mg

Talc 10 mg

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

2. Preparation of tablets

Neck Seed Extract or fraction 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

Neck Seed Extract or fraction 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

Neck Seed Extract or fraction 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

20 mg < RTI ID = 0.0 >

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

100 mg of the herb extract or fraction

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

100 mg of the herb extract or fraction

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 (8)

A pharmaceutical composition for the prevention or treatment of cognitive dysfunction comprising an extract of Sambuconoides as an active ingredient. The pharmaceutical composition according to claim 1, wherein the extract is selected from the group consisting of water, an alcohol having 1 to 4 carbon atoms, and a mixed solvent thereof. Composition. A pharmaceutical composition for preventing or treating cognitive dysfunction, comprising an organic solvent fraction prepared by further fractionating the neck extract of claim 1 with an organic solvent as an active ingredient. 4. The pharmaceutical composition according to claim 3, wherein the organic solvent is at least one selected from the group consisting of hexane, ethyl acetate and butanol. The method of claim 1, wherein the cognitive dysfunction is selected from the group consisting of Alzheimer's disease, cerebrovascular dementia, pick disease, Creutzfeldt-Jakob disease, dementia due to head injury, and Parkinson's wherein the compound is at least one member selected from the group consisting of: A food composition for preventing or ameliorating a cognitive dysfunction, which contains an extract of Momordica sativa as an active ingredient. A food composition for preventing or ameliorating a cognitive dysfunction, comprising an organic solvent fraction prepared by further fractionating the headache extract of claim 6 with an organic solvent as an active ingredient. 8. The food composition according to claim 7, wherein the organic solvent is at least one selected from the group consisting of hexane, ethyl acetate and butanol.

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