KR20190018897A - Composition for Prophylaxis and Treatment of Cognitive Disfuction or Improvement of Memory Comprising Fruit Bark Extract - Google Patents

Abstract

The present invention relates to a composition for preventing or treating memory impairment or cognitive dysfunction using waste resources containing a large amount of a useful substance and more particularly to a composition for preventing or treating memory or cognitive dysfunction And to a composition for preventing, treating, or ameliorating the aforementioned diseases.

Description

TECHNICAL FIELD The present invention relates to a composition for enhancing memory or cognitive dysfunction and a composition for preventing and treating cognitive dysfunction,

The present invention relates to a composition for preventing or treating memory impairment or cognitive dysfunction utilizing waste resources containing a large amount of useful substances.

In the flood of information that exponentially grows in modern society, cognitive function and memory have become important subjects from the youth to the elderly. Declining memory and cognitive dysfunction make social life itself as well as normal personal life impossible and cause a lot of social cost increase. Especially, in the case of dementia patients, the possibility of social life is known to have a major influence on the memory deterioration. In recent years, digital dementia, in which not only senile dementia but also cognitive functions such as memory and calculation ability are greatly reduced by relying on various digital devices such as mobile phones, PDAs, and computers, is also common in young people. Current treatments for dementia include galantamine, donepezil, and ribastigmine, but they have side effects such as gastrointestinal side effects, dizziness, and headache. Among these, galantamine is a herbal medicine ingredient extracted from snowdrop of Bulgarian wild plant, and it is a typical dementia treatment agent having choline esterase inhibitory effect together with donepezil and ribastigmine. However, the US Food and Drug Administration (FDA) has reviewed safety studies based on two studies that have used this drug in the treatment of mild cognitive dysfunction based on a study showing higher mortality among people treated with this drug.

Dementia refers to a disease that prevents normal daily living in the occupational, social and interpersonal relationships due to mild memory impairment, general cognitive decline, emotional disturbance, personality disorder, and behavioral disorders. Alzheimer's dementia accounts for about 50% of all dementia, and cognitive dysfunction due to Alzheimer's dementia is due to severe damage to the parasympathetic nerve that plays an important role in learning and memory and the reduction of the neurotransmitter acetylcholine It is known.

Thus, induction of cholinergic dysfunction is suggested as an effective experimental model for reducing cognitive impairment in humans. Since scopolamine is an antimuscarinic effect on the acetylcholine receptors in the body, it increases the activity of acetylcholinesterase and decomposes acetylcholine in the nerve junctions to decrease cognition. Therefore, evaluation of new anti-dementia drugs Which is widely used in experimental models.

On the other hand, studies have been conducted to improve cognitive function by activating the cholinergic action of the brain using a cholinergic agent, an acetylcholine precursor, and an acetylcholinesterase inhibitor.

Japanese Patent Registration No. 10-1095034 discloses that the extract of aquaculture extracts inhibits the activity of acetylcholinesterase and reports the usefulness of the extract of Seaweed extract as a composition for preventing or treating dementia and improving cognitive function. Japanese Patent Application Nos. 10-1438415, 10-1194974 and 10-0730302 disclose the use of scopolamine-induced learning and memory-deprivation mouse models to inhibit the production of natural products such as horseradish extract, chrysanthemum extract, Derived extracts have been shown to be effective in improving memory and preventing and treating cognitive dysfunction.

On the other hand, fruit husks discarded as wastes contain a large amount of useful physiologically active ingredients such as minerals, vitamins, and polyphenols, so that there is a possibility of developing pharmaceutical or functional food compositions using fruit husk by-products. The development of fruit peel-derived products can reduce the cost of waste disposal and reduce the environmental pollution caused by the waste treatment process.

Patent No. 10-1095034 Registration No. 10-1438415 Patent No. 10-1194974 Patent No. 10-0730302

It has been used for many years as a food resource, and has been established for safety of the human body. Although it contains a large amount of useful substances, research on usability is poor due to poor sensory properties and by identifying the physiological activity of resources that have been discarded as byproducts It is intended to provide a composition for preventing and treating new memory impairment or cognitive dysfunction that can be safely used.

In order to accomplish the above object, the present invention relates to a pharmaceutical composition for preventing or treating memory impairment or cognitive dysfunction, which comprises an extract of apple peel or pear shell.

The composition of the present invention has an effect of inhibiting the activity of acetylcholinesterase and has an effect of improving cognitive function by activating the cholinergic action of the brain. Also, apples and pears have a problem of roughness, roughness and sourness, and a lot of taste sensation. They prefer to eat shells by removing the skin from the flesh by avoiding the consumption of shells. However, they have been edible from ancient times. Can be used.

In particular, the mixed extracts of apple peel and pear peel showed inhibitory activity of acetylcholinesterase compared to each of apple peel and pear peel extract, and in the experiment of scopolamine induced animal model, Lt; / RTI > This is expected to be due to the synergistic effect of the interaction between the components contained in the extract.

 In the present invention, an apple peel or an extract of a pear skin can be obtained by directly extracting an apple peel or a pear peel or a mixture thereof (hereinafter, referred to as a 'fruit peel') or using a separate solvent. Fruit peel means the portion of the fruit that has been removed from the fruit, but it is natural that some of the fruit may be included. When extracting using a separate solvent, water, C1-C4 lower alcohol or a mixture thereof may be used as the solvent. The fruit husks may be used as the raw material itself or may be dried, and it is more preferable to extract the fruits by crushing or grinding to facilitate extraction. Any of the methods used in the art for extracting natural products may be used for the extraction, and for example, cold-water extraction, heat extraction, ultrasonic extraction, etc. may be used, but the present invention is not limited thereto. The extract obtained by extraction using a juice or a solvent can be used as such, concentrated, or dried. It is a matter of course that conventional drying methods such as spray drying, thermal drying and freeze drying can be used.

The composition of the present invention can be used for preventing or treating cognitive dysfunction caused by diseases as well as improvement of memory ability and learning ability of a normal person. Diseases that result in cognitive dysfunction include, but are not limited to, Alzheimer's, Parkinson's disease, dementia, cranial nerve disease, attention deficit, brain ischemia, depression, drug addiction, traumatic brain injury.

The composition of the present invention may be prepared by a method known in the pharmaceutical field for use as a therapeutic agent and may be prepared by mixing with a carrier or a pharmaceutically acceptable carrier, a forming agent, . The composition of the present invention can be formulated into a preparation for oral or parenteral administration, and can be used as a preventive and therapeutic agent for memory enhancement or cognitive dysfunction. The dose of the active ingredient according to the present invention can be appropriately selected depending on the degree of absorption of the active ingredient in the body, the form of the preparation, the age, sex and condition of the patient, the degree of symptoms, etc., , And may be administered in divided doses. Typical dosages are 0.001 mg / kg · day to 10 g / kg · day. The composition of the present invention can be safely used without toxicity and side effects, so that it can be safely used for prolonged use for preventive purposes.

The present invention also relates to a health food composition for preventing or ameliorating memory impairment or cognitive dysfunction, comprising an extract of apple peel or cheek skin. Even when used as a health food composition, a more advantageous effect can be expected when a mixed extract of an apple skin and a pear skin is used. The fruit skin extract may be added to the health functional food of the present invention in an amount of preferably 0.01 to 100% by weight. The fruit shell extract has a fruit-derived flavor, so that it is excellent in the sensory property without any special sweetness, and can be easily ingested. The health functional food of the present invention includes forms such as tablets, capsules, pills, and liquids, and examples of foods to which the composition of the present invention can be added include various foods, beverages, gums, tea, vitamins , And health functional foods.

As described above, according to the composition of the present invention, the effect of inhibiting the activity of acetylcholinesterase in brain tissue is excellent, and in the experimental model of cognitive dysfunction induced by scopolamine, the effect of improving cognitive function is excellent, May be useful for the prevention and treatment of cognitive dysfunction.

The composition of the present invention utilizes an extract of a fruit shell which has not been reported for toxicity even when it is widely used for a long time, and can be safely used even when a long-term large dose is taken for the purpose of prevention, without worrying about side effects accompanying it.

Furthermore, the present invention is based on the new efficacy of the fruit skin which has been discarded as a by-product of fruit due to the problem of the sensibility, although it is known that the useful substance is contained, and it is an extremely useful invention in terms of environment of resource recycling.

1 is a graph showing the acetylcholinesterase inhibitory activity of the composition of the present invention.
Figure 2 is a graph showing the effect of the composition of the present invention on stop-through latency in a submultiple test.
Figure 3 is a graph showing the effect of the composition of the present invention on distance-through latency in a Sumi-Test.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, these embodiments are merely examples for explaining the content and scope of the technical idea of the present invention, and thus the technical scope of the present invention is not limited or changed. It will be apparent to those skilled in the art that various changes and modifications can be made within the scope of the technical idea of the present invention based on these examples.

[Example]

Example 1: Preparation of fruit peel extract

Apples and pears were purchased in the agricultural and marine products wholesale market between April and July 2016. After washing, the water was removed and the skin was peeled and dried. The dried sample was placed in an internal vessel of a heat treatment apparatus (JISCO, Korea) capable of withstanding a pressure of 10 kg / cm 2 with 6 times (w / w) water and heat-treated at 90 ° C for 2 hours. The heat treatment apparatus heated the sample at a predetermined temperature and time by inserting the fruit into the outer container to prevent carbonization of the sample due to direct heat transfer. After 2 hours, the extract was concentrated to a certain concentration, lyophilized and stored in a refrigerator.

Example 2 Evaluation of acetylcholinesterase inhibitory activity in brain tissue

(AB, Apple Bark), PB (Pear Bark), 1: 1 (w / w) mixed extract (BF, Bark Formulation) of apple peel and pear skin prepared by the method of Example 1 ) Was evaluated by using the Ache assay kit (abcam, ab138871). The inhibitory activity of acetylcholinesterase (ACE)

In order to obtain the brain tissue of the mouse, the brain tissue was immersed in the assay buffer and pulverized. Then, the supernatant was separated by centrifugation at 1500 × g for 5 minutes. Fruit bark extract was added to brain supernatant at a concentration of 5 ~ 500 ㎍ / ㎖ and treated at room temperature for 1 hour. According to the manufacturer's manual, the reaction solution was treated with the assay sample, shaded, reacted for 30 minutes in the room, and the absorbance at 410 nm was measured. The AchE inhibition rate (%) was calculated from the absorbance measured by the following formula.

Inhibition rate (%) = 1 - (absorbance of sample group / absorbance of no addition group) x 100

FIG. 1 is a graph showing the results. The AchE inhibitory activity of the apple bark extract was not significantly different depending on the concentration, whereas the AchE inhibitory activity of the bark peel extract was concentration-dependent. At low concentration of 5 ~ 50 ㎍ / ㎖, the AchE inhibitory activity of the apple peel extract was superior to that of the bark peel extract, but the AchE inhibitory activity of the bark peel extract was remarkable at the concentration of 100 ㎍ / ㎖ or more.

Especially, the mixed extracts of the bark and apple bark showed higher synergistic effect than the extracts of apple bark or bark alone, due to the interactions between the components due to the high AchE inhibitory activity. Increase in the number of workers.

Example 3: Supramolecular-induced learning and memory-depressed mice.

7 weeks old C57bl / 6 mice were purchased from BioLink. The test animals were fed with standard diet (crude protein 22.1% or higher, crude fat 8.0% or less, crude fiber 5.0% or less, whey protein 8.0% or less, calcium 0.6% or more, phosphorus 0.4% or more, After being purified for 1 week in laboratory environment, it was used for the experiment.

After 1 week of refinement, mice with good health status were selected and repeated for 5 days once a day in Morris water maze for 1 week. Morris Sumiro was a water tank with a diameter of 90 cm and a height of about 30 cm. It was made by filling a 2/3 tap water with a water temperature of 27 ° C and installing a cylindrical platform with a diameter of 10 cm on which a mouse could rise. Mice that went up from the pool to the platform within 30 seconds of learning once a day were selected and classified into a control group and a fruit skin extract administration group (200 mg / kg) in a group of 10 mice selected. Thereafter, repeated administration of apple bark extract, bark extract, or mixed extract of apple husk and bark were administered to the fruit bark extract group for one week with orally administered to the platform three times a week .

After 14 days of training and 7 days of drug administration, scopolamine (1 mg / kg) was intraperitoneally injected into each experimental group 30 minutes later. After 30 minutes, mice were added to the Morris water maze and the behavior was measured by VIDEOTRACK , And analyzed with videotrack software.

FIG. 2 shows the stop-through latency of a mouse from the pool to the platform after scopolamine treatment, and FIG. 3 shows the distance-through latency of the pool until it rises from the pool to the platform will be. FIGS. 2 and 3 show that the extract of apple bark or bark greatly reduces the latency of treatment with scopolamine, and that the mixed extract of apple bark and bark skin has a synergistic effect . This was in agreement with the result shown in Fig.

Claims (6)

A pharmaceutical composition for preventing and treating memory enhancement or cognitive dysfunction, comprising an extract of an apple bark or a bark.
The method according to claim 1,
A pharmaceutical composition for preventing and treating memory impairment or cognitive dysfunction, comprising a mixed extract of an apple skin and a pear shell.
The method according to claim 1,
The pharmaceutical composition for preventing and treating memory impairment or cognitive dysfunction according to claim 1, wherein the extract is extracted with water or water or a C1 to C4 lower alcohol or a mixed solvent thereof.
4. The method according to any one of claims 1 to 3,
Wherein the cognitive dysfunction is caused by Alzheimer's disease, Parkinson's disease, dementia, cranial nerve disease, attention deficit disorder, brain ischemia, depression, drug addiction, traumatic brain injury.
A health food composition for preventing or ameliorating memory impairment or cognitive dysfunction, comprising an extract of apple bark or cheek skin.
6. The method of claim 5,
A health food composition for preventing or ameliorating memory impairment or cognitive dysfunction, comprising a mixed extract of apple peel and pear shell.

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