KR100950254B1 - Composition having congnition enhancing activity comprising Betula Platy Phylla extract - Google Patents

Abstract

The present invention relates to a composition having brain and cognitive function improving activity, and more particularly to a composition for improving brain function and cognitive function containing a lower alcohol extract and / or fractions thereof of the birch bark as an active ingredient. .

Description

Composition having congnition enhancing activity comprising Betula Platy Phylla extract}

The present invention relates to a composition having brain and cognitive function improving activity, and more particularly to a composition for improving brain function and cognitive function containing a lower alcohol extract and / or fractions thereof of the birch bark as an active ingredient. .

As senile dementia has recently been recognized as a degenerative central nervous system disease and the number of patients has increased day by day, it has emerged as a big social problem, and the importance of its prevention, improvement and treatment is newly emerging. Alzheimer's disease is known to be the majority of dementia patients that have recently emerged as social problems. Alzheimer's disease patients suffer from abnormalities in almost all nerves, including cholinergic, adrenergic, GABA and glutamate nerves, and the loss of cholinergic nerves is known to be most serious. Therefore, researches for the development of Alzheimer's disease treatments have been actively conducted to restore or improve cholinergic disorders.

The development of a cure for Alzheimer's disease has been advanced as the method of artificially manipulating the condition similar to Alzheimer's disease by inducing abnormalities in the cholinergic nervous system by administering scopolamine to experimental animals (Flood, J.). and Cherkin, A. Scopolamine effects on memory retention in mice, Behav. Neural. Biol. 45: 169-184 (1986)).

The administration of scopolamine in rats is associated with symptoms similar to those in Alzheimer's disease, including degeneration of cholinergic neurons and loss of memory, as well as deficiencies in acquisition, immediate response, and working memory. Smith, 1988; Giacobini, E. and Cuadra, G. (1994)). These symptoms are Pizo, an acetylcholinesterase (AChE) inhibitor that maintains the concentration of acetylcholine in the cell by inhibiting the degradation of arecoline and oxotremorine or acetylcholine, which are agonists of cholinergic neurons. It was alleviated by the administration of physostigmine and the like. Indeed, tacrine, an AChE inhibitor, has been used in the clinic, but studies such as hepatotoxicity, short half-life, and low bioavailability have been raised.

The present inventors found that alcohol extracts and fractions of the bark of birch have significant brain and cognitive functioning activities while searching for dementia activity in natural products to find substances with new brain and cognitive functioning activities. Confirmed.

The birch (Betula Platy Phylla) of the present invention is a deciduous tree belonging to the birch family and grows in high mountains north of Gangwon-do but is also distributed in the North Sea of Japan and China. The bark is white and peeled horizontally, and the bark is dark brown with a branch. Leaves regenerate in the intestines and two in the complex. Triangular ovate, 5-7cm long, 4-6cm wide, with acute tip. It is a wide tongue or heart bottom and has a marginal value at the edge. There is almost no hair, but there are some hairs on the leaf fluid on the back of the leaf.

The bark of birch contains about 35% of betulin, about 35% of various higher fatty acids, and about 7% of tannin (about 11% of tannin in the endothelium). Fresh leaves also contain 0.25% of betufolifolientriol, tritereonides such as betufolifolientetraol and dammarantype triterpenoids, and tannins. 5.19%, and the department contain 11.44% essential oils. The bark of the Manchurian birch contains about 23% betulin. Birch bark is called 'baekhwapi' and herbal medicine is used as a painkiller or antipyretic and diuretic. However, until now, research on the brain function and cognitive function of birch and its components has not been conducted, and thus the present invention surprisingly confirms that the alcohol extract and its fraction of the birch bark exhibit the brain and cognitive function improving activity. The invention has been completed.

The present invention as the active ingredient comprises a C _{1 -4} alcohol extract of birch bark by itself, or provide for the brain and cognitive function improving composition comprising an excipient with a pharmaceutically acceptable or food significant.

The present invention also provides a brain function comprising the fraction obtained by fractionating the alcoholic extract with an organic solvent or water as an active ingredient, or by fractionating the fraction alone, or with a pharmaceutically or food-acceptable excipient. It provides a composition for improving cognitive function.

The present invention also provides a food additive, dietary supplement, or pharmaceutical composition exhibiting a brain and cognitive function-improving effect containing a composition comprising the lower alcohol extract and / or a fraction thereof of the birch bark. The dietary supplement or pharmaceutical composition is preferably selected from the group consisting of tablets, capsules, powders, granules, liquids and pills.

Hereinafter, the present invention will be described in detail with reference to an example of the extraction process of birch bark.

C _{1 -4} alcohol such as birch bark as methanol, ethanol, propanol, isopropanol or butanol, preferably a C _{1 -3} alcohol, more preferably from a conventional extract such as ultrasonic extraction with methanol, or ethanol as a solvent method Extracted with water, concentrated under reduced pressure to obtain an alcohol extract.

The birch bark alcohol extract of the present invention exhibits an excellent brain function and / or cognitive function improving effect, for this purpose may be administered to the alcohol extract itself, to increase the content of the active ingredient to obtain a better effect, the The extract may be fractionated with an organic solvent or water, or a fraction prepared by column chromatography may be administered. As the organic solvent for the preparation of the fraction of the solvent is usually used when a fraction herbal extracts, for example, C _{1 -4} alcohols, including butanol, hexane, ether, ethyl acetate, chloroform, dichloromethane, benzene, acetone, etc. Column chromatography may use conventional column chromatography, such as HP-20 column chromatography.

In the present invention, the Birch of the fraction C _{1 -4} fraction from an alcohol extract of the bark, especially CHCl ₃ fraction and BuOH fraction exhibited excellent brain function and cognitive function improving activity, such as the following examples.

The composition of the present invention exhibits an effect of improving brain function and cognitive function, and is used for the prevention and treatment of memory impairment, memory impairment, in particular memory impairment associated with deficiency of acquisition and / or loss of activity memory, dementia, forgetfulness, Alzheimer's disease, etc. It can be used as a composition.

The compositions of the present invention may be formulated by methods known in the pharmaceutical or food arts, and may be used alone or in admixture with pharmaceutically acceptable carriers, excipients, etc. For example, it may be formulated as a liquid, syrup, capsule, and the like, which may be administered orally or parenterally.

Liquids, capsules and the like comprising the composition of the present invention can be used as a dietary supplement, and the term "health supplement" used in the present invention is a tablet using a raw material or ingredients with useful functionality to the human body Refers to functional foods such as health foods or beverages, yogurt, cheese, etc. manufactured and processed in the form of capsules, powders, granules, liquids, pills, and the like.

The composition of the present invention is appropriately selected according to the absorption of the active ingredient in the body, the rate of excretion, the age and weight of the patient, the sex and condition, the severity of the disease to be treated, etc., but generally in adults 0.01 to 500 mg / kg, per day Preferably, the dosage is 0.1 to 200 mg / kg. The unit dosage form so formulated may be administered several times at regular time intervals as needed.

Hereinafter, the present invention will be described in more detail with reference to the following examples. These examples are for illustrative purposes of the present invention and are not intended to limit the protection scope of the present invention.

Example  One

1) Extraction and Fraction

800 g of dried birch bark was ultrasonically extracted with 80% EtOH to obtain an EtOH extract (84 g). By suspending them in water and fractionated by CHCl ₃ to CHCl ₃ to obtain fraction (5g). (See equation 1)

Equation 1. Extraction of birch and Fractionation

Example  2

840 g of dried birch bark was ultrasonically extracted with 80% MeOH to obtain a MeOH extract (63.7 g). It was suspended in water and fractionated with n-BuOH to give an n-BuOH fraction (15.2 g). (See Equation 2).

Equation 2. Extraction of Birch and Fractionation

Experimental Example  One

1. Experiment Method

1) Experimental Animal

Seoul National University experimental animal breeding room was supplied with 25-30g of ICR male (male) reared with sufficient water and feed was used for the experiment after being adapted to the laboratory environment for one week.

2) Passive avoidance test

Split the evacuation box (40 X 20 X 20 cm) with a 3 mm thick stainless steel bar at the bottom into a bright and dark room, and 0.2 mA / 10 g through the stainless bar when the mouse in the bright room enters the dark room. I trained to give an electrical stimulus of my weight. After 24 hours, the same test was performed to measure the time the mouse stays in a bright room (Step through latency), and compared with the drug-administered group as an index to remember the previous day's training. Dissolve scopolamine in physiological saline to prepare a 1.5mg / kg solution and inject it subcutaneously 30 minutes before training to cause memory and cognitive impairment. Birch bark alcohol extract, 1 hour 30 minutes before scopolamine chloroform The fractions and butanol fractions were orally administered to observe the effects on the memory and cognitive impairment induced by scopolamine.

The results are shown in Tables 1 and 2 and FIGS. 1 and 2.

Table 1. With scopolamine  Evaluation of Birch Bark in Measurement of Passive Evasion in Mice That Cause Memory Impairment Total Ethanol  Extracts and their CHCl ₃ In fractions  Memory recovery effect

Treatment (mg / kg) Step through latency (seconds) ^* (Step through latency) % Recovery Control 141.6 ± 59.5 100.0 Scopolamine 41.4 ± 24.6 0.0 Total Ethanol Extract 50 94.1 ± 49.4 52.6 Total Ethanol Extract 100 94.0 ± 68.2 53.0 CHCl ₃ Fraction 50 106.9 ± 65.7 65.4 CHCl ₃ Fraction 100 63.7 ± 38.7 22.2 Betulin 1 59.6 ± 48.8 18.2 Betulin 5 69.7 ± 60.0 28.3

* Values are mean ± S.D.

Table 2. With scopolamine  Evaluation of Birch Bark in Measurement of Passive Evasion in Mice That Cause Memory Impairment Total Methanol  Extracts and their BuOH In fractions  Memory recovery effect

Treatment (mg / kg) Step through latency (seconds) ^* (Step through latency) % Recovery Control 168.4 ± 23.0 100.0 Scopolamine 46.6 ± 34.9 0.0 Total Methanol Extract 50 119.2 ± 75.2 59.6 BuOH Fraction 10 70.2 ± 62.4 19.4 BuOH Fraction 50 125.2 ± 67.0 64.5 BuOH Fraction 100 103.7 ± 68.7 46.9 Betulin 5 73.3 ± 52.9 21.9

* Values are mean ± S.D.

As shown in Tables 1 and 2 and Figures 1 and 2, the total ethanol extract (50, 100 mg / kg, ip), total methanol extract of birch, the degree of recovery for scopolamine-induced memory and cognitive impairment (50 mg / kg, ip) and CHCl ₃ fraction of total ethanol extract (300 mg / kg, ip) and butanol fraction (50 mg / kg, ip) of total methanol extract were significantly increased. In particular, when the CHCl ₃ fraction of the ethanol extract was administered at a concentration of 50mg / kg showed the highest recovery rate of about 65%. From the above results, it can be seen that the alcohol extract and its fractions of the birch bark are excellent in improving brain function and cognitive function.

Composition Example

Composition example  1. Preparation of Capsule

200 mg of chloroform fraction of Example 1

Lactose 100mg

Starch 93mg

Talc 2mg

Magnesium stearate proper amount

The capsules are prepared by mixing the above components and filling gelatin capsules according to a conventional method for preparing capsules.

Composition example  2. Preparation of Capsule

100 mg butanol fraction of Example 2

Lactose 100mg

Starch 93mg

Talc 2mg

Magnesium stearate proper amount

The capsules are prepared by mixing the above components and filling gelatin capsules according to a conventional method for preparing capsules.

Composition example  3. Liquid  Produce

200 mg of methanol extract of Example 2

20 g of sugar

20 g of isomerized sugar

Lemon flavor

Add 100 ml of purified water

The above components are mixed according to a conventional method for preparing a liquid, and filled into 100 ml brown bottles and sterilized to prepare a liquid.

Composition example  4. Liquid  Produce

300 mg of ethanol extract of Example 1

20 g of sugar

20 g of isomerized sugar

Lemon flavor

Add 100 ml of purified water

The above components are mixed according to a conventional method for preparing a liquid, and filled into 100 ml brown bottles and sterilized to prepare a liquid.

Composition example  5. Manufacture of drinks

5 wt% ethanol extract of Example 1, 0.05 wt% food coloring, 0.05 wt% orange essence, 5.0 wt% fructose, 0.1 wt% citric acid, 0.05 wt% vitamin C prepared a composition containing a general functional beverage base Then, a suitable amount of purified water was added to prepare a beverage.

1 is a total ethanol extract of birch bark of the present invention and its CHCl ₃ A diagram showing the effect of memory recovery on fractions,

Figure 2 is a total methanol extract of the birch bark of the present invention and BuOH A diagram showing the effect of memory recovery on fractions.

Claims (7)

A dietary supplement for improving cognitive function comprising C _1-4 alcohol extract of birch bark alone as an active ingredient, or with a food acceptable excipient. A dietary supplement for improving cognitive function comprising an organic solvent fraction of C _1-4 alcohol extract of birch bark alone as an active ingredient, or with a food acceptable excipient. The dietary supplement for improving cognitive function of claim 2, wherein the fraction is a fraction of at least one solvent selected from butanol, hexane, ether, ethyl acetate, chloroform, dichloromethane, benzene, and acetone. delete delete The dietary supplement for improving cognitive function according to claim 1 or 2, wherein the dietary supplement is selected from the group consisting of tablets, capsules, powders, granules, liquids, pills and beverages. delete

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