KR20220046907A - Composition for preventing, alleviating or treating cognitive disorder by climacterium comprising fabaton soybean leaf extract as effective component - Google Patents

Abstract

The present invention relates to a composition for preventing, alleviating, or treating cognitive disorder by climacterium containing a Fabaton soybean leaf extract as an effective component. According to the present invention, with respect to a climacterium animal model group administered with an Fabaton soybean leaf extract, which is an effective component of the composition of the present invention, a spontaneous turnover rate is increased in a Y-maze behavioral analysis and movements to find a platform is reduced in a water maze behavioral analysis, and a retention time in a quadrant where the platform was located is increased. Thus, it is proved that the Fabaton soybean leaf extract has effects of increasing learning ability and memory cognitive function. Accordingly, the Fabaton soybean leaf extract can be used as a health functional food and medicine effective for cognitive impairment caused by climacterium.

Description

Fabaton soybean leaf extract as an active ingredient for preventing, improving, or treating cognitive impairment due to menopause, the composition for preventing, alleviating or treating cognitive disorder by climacterium comprising fabaton soybean leaf extract as effective component

The present invention relates to a composition for preventing, improving, or treating cognitive impairment due to menopause comprising a pabaton bean leaf extract as an active ingredient.

Menopause, also called menopause, refers to the period of transition from maturity as a woman to old age in view of the function of the ovaries. The age of menopause varies from person to person depending on constitution, nutritional status, and frequency of childbirth, but is statistically considered to be 40 to 55 years old. The prolongation of life expectancy tends to delay menopause slightly. And pregnant women tend to be late, and unmarried women tend to be relatively early. At menopause, the amount or cycle of menstruation becomes irregular due to ovarian dysfunction, and menstruation is finally abolished due to a decrease in the secretion of follicular hormone (estrogen) over several months to three years. It causes ataxia and causes menopausal disorders. In addition, it causes the anterior pituitary gland to malfunction, and the adrenocorticotropic hormone (ACTH) abnormally stimulates the adrenal cortex to compensate. Malfunctions characteristic of menopause appear, such as bringing abnormalities to function and leading to obesity. A series of syndromes called menopausal disorders appear in both physical and mental aspects, such as atrophy of the genitals and changes in blood pressure. That is, hot flashes, palpitations (heart beating harder than usual), dizziness, tinnitus, high blood pressure, digestive disorders, headache, memory loss, depression, etc. They range from mild enough to cause no disturbance to severe enough to cause you to lie down. About 30% are receiving treatment, but usually they get better on their own within 1 to 2 years, and treatment is mainly hormone replacement.

Among the mental disorders caused by menopause, mild cognitive impairment such as memory loss or learning ability is a state in which memory or learning ability is clearly decreased in objective tests, but the ability to carry out daily life is preserved and is not dementia. Of these, 10-15% progress to dementia, so early detection and treatment are very important.

The first characteristic of mild cognitive impairment is the presence of obvious cognitive decline. This cognitive decline is mainly a decrease in memory, but it may not be the case. Although daily life movements and functional levels are largely preserved, there are cases where it is uncomfortable to maintain instrumental daily life movements. Along with cognitive decline, various types of psycho-behavioral symptoms are also more commonly observed in the normal elderly. The most common symptoms are malaise, apathy, and anxiety. Psychotic symptoms such as delusions or hallucinations are known to be rare in patients with mild cognitive impairment.

On the other hand, Pabaton soybean leaves contain a high content of isoflavone derivatives by treating soybean leaves with ethylene, an ethylene donor or an ethylene generator. This is disclosed.

As a technology related to the menopausal syndrome of Pabaton bean leaf, Korean Patent No. 1965059 discloses a method for producing a Pabaton bean leaf composition containing daidzein and genistein in high content, and an active ingredient fortified bean leaf composition for improving menopausal syndrome manufactured using the same However, it has not been disclosed yet for a composition for preventing, improving or treating cognitive impairment due to menopause comprising the pabaton bean leaf extract of the present invention as an active ingredient.

The present invention has been derived from the above needs, and the present invention provides a composition for preventing, improving or treating cognitive impairment due to menopause comprising Pabaton soybean leaf extract as an active ingredient, and the active ingredient of the present invention In the Y-maze behavior analysis of the menopause animal model group administered with the baton bean leaf extract, the spontaneous rotation rate increased, and the movement to the platform was reduced in the water maze behavior analysis, as well as the retention time in the quadrant where the platform was increased. By confirming that it improves the cognitive function of learning ability and memory, the present invention has been completed.

In order to achieve the above object, the present invention provides a health functional food composition for preventing or improving cognitive impairment due to menopause comprising Pabaton soybean leaf extract as an active ingredient.

In addition, the present invention provides a pharmaceutical composition for preventing or treating cognitive impairment due to menopause comprising Pabaton bean leaf extract as an active ingredient.

The present invention relates to a composition for preventing, improving or treating cognitive impairment due to menopause comprising Pabaton bean leaf extract as an active ingredient, and Y- The effect of improving the cognitive function of learning ability and memory by increasing the spontaneous rotation rate in the maze behavior analysis and reducing the movement to the platform in the underwater maze behavior analysis, as well as increasing the retention time in the quadrant where the platform was there will be

1 is a result of confirming the changes in body weight (A) and feed intake (B) according to the diet of pabaton bean leaf extract of the present invention in a menopause animal model induced by resection of the ovaries.
2 is a Y-maze behavioral analysis result in a menopause animal model induced by excising the ovaries according to a diet with a pabaton bean leaf extract of the present invention. * indicates that the spontaneous alternation rate (%) of the ovariectomy-induced menopausal group (OVX) was statistically significantly decreased compared to the control group (CTL), p<0.05, and # is the ovariectomy-induced menopausal group The spontaneous alternation rate (%) of the Pabaton soybean leaf extract diet group (OVX+PD) of the invention was statistically significantly increased, p<0.05.
3 is a water maze experiment of a menopause animal model fed with pabaton bean leaf extract of the present invention, confirming the movement of learning for 4 days to find the platform. * indicates that the movement time to find the platform of the menopausal induction group by ovariectomy (OVX) increased statistically significantly compared to the control group (CTL), p<0.05, and # is the present invention compared to the menopausal induction group by ovariectomy The movement time to find the platform of the pabaton bean leaf extract diet group (OVX+PD) of Pabaton soybean leaf extract was statistically significantly reduced, p<0.05.
Figure 4 confirms the time spent in the quadrant where the platform was after removing the platform in the water maze experiment of the menopause animal model fed with the pabaton bean leaf extract of the present invention. * indicates that the time to stay in the platform quadrant of the ovariectomized menopausal group (OVX) was statistically significantly decreased compared to the control group (CTL), p<0.05, and # is compared to the menopausal induction group by ovariectomy The staying time in the quadrant with the platform of the pabaton soybean leaf extract diet group (OVX+PD) of the present invention was statistically significantly increased, p<0.05.

The present invention relates to a health functional food composition for preventing or improving cognitive impairment due to menopause, comprising Pabaton soybean leaf extract as an active ingredient.

The pabaton soybean leaf extract comprises the steps of (1) treating soybean leaves with ethylene, an ethylene donor, or an ethylene generator in an amount of 5 to 500 μg/ml; (2) after step (1), extracting by adding an extraction solvent to soybean leaves; (3) filtering the extract of step (2); And (4) drying the filtered extract of step (3) under reduced pressure; preferably obtained by an extraction method comprising, but not limited thereto.

The ethylene donor in step (1) of the extraction method of Pabaton soybean leaves is preferably, but not limited to, ethephon, and the extraction solvent in step (2) is water, C ₁ to C ₄ lower alcohol Or a mixture thereof is preferable, but not limited thereto, and the extraction method is preferably extracted by any one extraction method selected from filtration, hot water extraction, immersion extraction, reflux cooling extraction, and ultrasonic extraction, but all known in the art A conventional extraction method may be used. The extraction solvent is preferably added by adding 1 to 20 times the weight of the dried pabaton soybean leaves, more preferably 5 to 15 times. The extraction temperature is preferably 90 ~ 120 ℃, but is not limited thereto. In addition, the extraction time is preferably 3 to 10 hours, more preferably 5 to 7 hours, but is not limited thereto. In the above method, it is preferable to use a vacuum vacuum concentrator or a vacuum rotary evaporator for the vacuum concentration in step (4), but is not limited thereto. In addition, drying under reduced pressure, vacuum drying, boiling drying, spray drying or freeze drying is preferable, but is not limited thereto.

The cognitive impairment due to the menopause is characterized by a decline in memory or learning ability.

The pabaton bean leaf extract is preferably prepared in any one formulation selected from beverages, pills, tablets, capsules, and powders, but is not limited thereto.

The health functional food composition of the present invention may be used with pabaton bean leaf extract as it is or with other foods or food ingredients, and may be appropriately used according to a conventional method. There is no particular limitation on the type of the health functional food composition. Examples of foods to which the pabaton bean leaf extract can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, tea , drinks, alcoholic beverages, and vitamin complexes, and includes all health functional foods in the ordinary sense. A health drink including the composition of the present invention may contain various flavoring agents or natural carbohydrates as additional ingredients like conventional drinks. The above-mentioned natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetener, natural sweeteners such as taumartin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like can be used. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 g of the composition of the present invention. The health functional food composition of the present invention includes, in addition to the active ingredients, various nutrients, vitamins, electrolytes, flavoring agents, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, and preservatives. , glycerin, alcohol, a carbonation agent used in carbonated beverages, and the like may be further contained. In addition, it may further contain the pulp for the production of fruit juice or vegetable beverage. These components may be used independently or in combination. The proportion of these additives is not very important, but is generally selected in the range of 0.01 to 2 parts by weight based on 100 parts by weight of the composition of the present invention.

In addition, the present invention relates to a pharmaceutical composition for preventing or treating cognitive impairment due to menopause comprising a pabaton bean leaf extract as an active ingredient.

The pharmaceutical composition of the present invention may be in various oral or parenteral formulations. In the case of formulation, a pharmaceutically acceptable carrier, excipient or diluent may be further included in addition to the active ingredient, and a diluent or excipient such as a generally used filler, extender, binder, wetting agent, disintegrant or surfactant is used. can be formulated. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and such solid preparations include one or more compounds and at least one excipient, for example, starch, calcium carbonate, sucrose or lactose, gelatin, etc. prepared by mixing In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid formulations for oral administration include suspensions, solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. there is. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As the base of the suppository, Witepsol, Macrogol, Tween 61, cacao butter, laurin fat, glycero gelatin, etc. can be used.

The pharmaceutical composition of the present invention may be administered orally or parenterally, and when administered parenterally, external or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebrovascular injection may be selected. The pharmaceutical composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is the type, severity, and drug activity of the patient. , can be determined according to factors including sensitivity to drug, administration time, administration route and excretion rate, duration of treatment, concurrent drugs, and other factors well known in the medical field. The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or may be administered in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered single or multiple. In consideration of all of the above factors, it is important to administer an amount that can obtain the maximum effect with a minimum amount without side effects, which can be easily determined by those skilled in the art.

The dosage of the composition of the present invention varies depending on the patient's weight, age, sex, health status, diet, administration time, administration method, excretion rate and severity of disease, and the daily dosage is the amount of pabaton bean leaf extract Based on 0.01 ~ 3,000 mg / kg, preferably 1000 ~ 2000 mg / kg, may be administered 1 to 6 times a day. The pharmaceutical 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.

Hereinafter, the present invention will be described in more detail using examples. These examples are only for illustrating the present invention in more detail, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not limited thereto.

Example 1. Preparation of pabaton bean leaf extract

Pabaton soybean leaves were prepared by treating soybean leaves with ethylene or Esepone, an ethylene donor, according to the method disclosed in Korean Patent No. 1451298. Soybeans were grown in the greenhouse for about 60 days until reaching the maximum growth stage (R3), where pod development occurs.

In step R3, 250 μg/ml of ethephon solution was applied to the cultivated soybean leaves twice every 24 hours. After 96 hours, soybean leaves were harvested, cut into small pieces, and dried at 35°C. The dried soybean leaves were mixed with water in a weight ratio of 1:10 and extracted at 100° C. for 6 hours. It was then lyophilized and stored at -20°C until use.

Example 2. Confirmation of changes in body weight and feed intake

8-week-old female C57BL mice were purchased (Coatec Co., Ltd., Pyeongtaek, Korea), and after a one-week adaptation period, both oocytes were excised. After ovariectomy, there was a recovery period for one week.

Experimental animals were a control group without ovarian resection (CTL, n=10), a group with ovarian resection (OVX, n=9), and a group fed with pabaton extract powder after ovarian resection (18.8 g/kg of fabacon). Soybean leaf extract diet, OVX+PD, n=10) was classified. All experimental animals were temperature-controlled for the entire period of 18 weeks, and 3-4 animals were bred per cage in a room with light from 06:00 to 18:00. Feed and water were fed ad libitum, and body weight and feed intake were evaluated every other day. The experimental animals used in the present invention were used according to the guidelines of the National Institutes of Health and the approved protocol (GLA-100917-M0093) of the Gyeongsang National University Institutional Animal Care and Use Committee.

As a result, as shown in FIG. 1 , the feed intake of the normal control group (CTL), the ovarian resection and general diet group (OVX), and the ovary resection and Pabaton soybean leaf extract diet group (OVX+PD) were at almost similar levels. However, in the case of body weight, in the normal group, the body weight increased only slightly, but there was little change in the number of days. increased significantly.

Example 3. Behavior analysis

Behavioral analysis was performed through the Y-maze and water maze test (Moris Water Maze test) using the experimental animals prepared in Example 2 above. Mobility stress was minimized by moving the experimental animals to the laboratory 30 minutes before the behavioral analysis experiment.

(1) Y-maze experiment

Each mouse was placed on one arm (position B) facing the center of the maze and allowed to move the Y-maze device for 8 min. Entering the arm was considered only when all four paws of the experimental animal entered the arm. and spontaneous rotation rate (%) was defined as consecutive items on three different arms, divided by the total number of possible trials. The movements of the experimental animals were recorded and analyzed with an animal behavior video program (EnthoVision).

As a result, as shown in FIG. 2, the spontaneous alternation rate of the ovary-resected general diet group (OVX) was statistically significantly reduced compared to the spontaneous alternation rate of the normal control group (CTL), but the Pabaton bean leaf extract of the present invention was In the ovariectomized group (OVX+PD), it was confirmed that the spontaneous alternation rate recovered (increased) statistically significantly again.

(2) Underwater maze experiment

The mice used in the water maze experiment were first trained to find an invisible platform randomly located in a 120cm-diameter swimming pool maintained at a temperature of 24±1℃ and a brightness of 200 Lux. All rats were trained 4 times daily for 4 consecutive days.

Motions for 90 seconds were recorded and analyzed with an animal behavior video program (Wageningen, Netherlands, Noldus Information Technology, EthoVision). On the 5th day, the platform was removed, and the time to enter the target quadrant where the platform was during training was analyzed.

As a result, as shown in FIG. 3 , on the first day, when visiting the platform, the degree of movement was normal control (CTL), ovariectomy + normal diet group (OVX), and ovariectomy + Pavaton bean leaf extract diet group (OVX + PD). It was similar, but after learning for 4 days, it was confirmed that there was a difference in the movement to find the platform. The ovariectomized group fed the pabaton bean leaf extract of the present invention moved more than the normal group, but found a platform. was confirmed.

In addition, as shown in Figure 4, in the 5th day experiment with the platform removed, the normal control group and the ovariectomized group fed the pabaton bean leaf extract of the present invention were looking for the quadrant where the platform was with a similar level of movement, but the general diet In one ovariectomy group, not only did the movement slow down, but they could not remember the quadrant where the platform was, so movement in the other quadrant appeared.

Claims (7)

A health functional food composition for preventing or improving cognitive impairment due to menopause comprising Pabaton soybean leaf extract as an active ingredient. The method according to claim 1, wherein the Pabaton soybean leaf extract comprises the steps of: (1) treating soybean leaves with ethylene, an ethylene donor or an ethylene generator in an amount of 5 to 500 μg/ml;
(2) after step (1), extracting by adding an extraction solvent to soybean leaves;
(3) filtering the extract of step (2); and
(4) A health functional food composition for preventing or improving cognitive impairment due to menopause, characterized in that it is obtained by an extraction method comprising; (4) drying the filtered extract of step (3) under reduced pressure. [Claim 3] The health functional food composition for the prevention or improvement of cognitive impairment due to menopause according to claim 2, wherein the ethylene donor in step (1) is ethephon. According to claim 2, wherein the extraction solvent in step (2) is water, C ₁ ~ C ₄ Health functional food composition for the prevention or improvement of cognitive impairment due to menopause, characterized in that it is a lower alcohol or a mixture thereof. According to claim 1, wherein the cognitive impairment due to menopause is a health functional food composition for the prevention or improvement of cognitive impairment due to menopause, characterized in that the decline in memory or learning ability. A pharmaceutical composition for the prevention or treatment of cognitive impairment due to menopause comprising Pabaton bean leaf extract as an active ingredient. [Claim 7] The pharmaceutical composition for preventing or treating cognitive impairment due to menopause according to claim 6, further comprising a pharmaceutically acceptable carrier, excipient or diluent in addition to the active ingredient.

Images