KR20210133603A - Composition for preventing or treating dementia comprising grub as active component - Google Patents

Abstract

The present invention relates to a novel composition for preventing or treating dementia caused by degenerative brain lesions such as Alzheimer's dementia, vascular dementia, and the like by administering grub powder. The composition has an excellent effect of increasing spatial working memory, increasing visual recognition memory, increasing associative learning ability, improving hippocampal cholinergic nervous system functions, suppressing Iba-1-IR positive responses of microglia, and suppressing the production of amyloid plaques in an Alzheimer's animal model. Accordingly, the composition is very useful in preventing, alleviating and treating Alzheimer's disease, has an effect of protecting brain damage tissues caused by cerebral ischemia, and thus can be utilized in preventing and treating vascular dementia.

Description

Composition for preventing or treating dementia comprising grub as active component

The present invention relates to a novel composition for preventing or treating dementia caused by degenerative brain lesions such as Alzheimer's dementia and vascular dementia by including slugs as an active ingredient.

Alzheimer's is a disease characterized by histological features of amyloid plaques and neurofibrillay angles in the hippocampus and cortex (Neuron, 6, 487-498). The most important process in the pathogenesis of Alzheimer's is It is a process of accumulation of insoluble beta-amyloid (Aβ) peptides.

Among the water-soluble beta-amyloid peptides, Aβ(1-40) and Aβ(1-42) are the most abundant, and Aβ(1-42) is more toxic than Aβ(1-40) because it is more likely to aggregate into amyloid plaques. (Acta Biolchm Pol, 52, 417-423) In addition to this, differences in genes such as amyloid precursor protein (APP), presenilin (PS)-1, PS-2, apolipoprotein, and oxidative sex in Alzheimer's (BBA, 2007, 285-297), which is confirmed by establishing an animal model of Alzheimer's by using various genetically engineered animals, for example, APP-expressing mice or by centrally administering a toxic Aβ peptide.

Oxidative damage caused by the accumulation of insoluble Aβ is known as one of the major etiologies of Alzheimer's, and an increase in oxidative damage markers in brain tissue of Alzheimer's patients (Neurochem Res 33, 450-458; Neurotox Rex 2, 67-168) and endogenous antioxidant system abnormalities (Neurotox Rex 2, 167-168) have been reported, and this phenomenon has also been reported in animal models of Alzheimer's disease (Behav Brain Res, 155, 185-196; J Neurosci, 27, 5394-5404).

In addition, damage and deterioration of the cholinergic system in the hippocampus and cortex contributes to cognitive memory decline, a characteristic symptom of Alzheimer's (Neurology 51, S18-S29; Curr Alzheimer Res 1, 241-248). .

On the other hand, as a prior art for the prevention or treatment of Alzheimer's, 3-amino-1-propanesulfonic acid and a neuroprotective agent or Co-administration with a neurotrophic agent is disclosed, and Korean Patent Application Laid-Open No. 10-2012-48105 discloses a pharmaceutical composition having a synergistic Alzheimer's therapeutic effect by combining ursodeoxycholic acid and ginkgo leaf extract.

In addition to this, various inventions related to compositions for treating Alzheimer's disease or pharmaceutical use have been made, but development of various drugs useful for Alzheimer's treatment is still required.

In addition, vascular dementia is mostly caused by damage to brain cells due to insufficient blood supply to various parts of the brain due to cerebrovascular arteriosclerosis. Although a drug that protects vascular dementia is used, it does not show a clear effect, and the existing dementia treatment mainly has an acetylcholinesterase inhibitory effect.

1. Korean Patent Publication No. 10-20.05-0101537 2, Korean Patent Publication No. 10-2012-48105

The present inventors tried to develop a drug that exhibits efficacy against degenerative brain lesions such as Parkinson's disease, Alzheimer's dementia, and vascular dementia. The present inventor completed the present invention by confirming the effect of slugs on Alzheimer's dementia and vascular dementia as a result of intensive research. Therefore, the technical task of the present invention is to prevent dementia caused by degenerative brain lesions such as Alzheimer's dementia, vascular dementia, etc. To provide novel compositions for treatment.

The present invention in order to achieve the above technical problem,

It provides a functional food composition for preventing or alleviating symptoms of dementia, comprising, as an active ingredient, any one or more selected from the group consisting of slug dry powder, slug blood lymph, and slug fermented broth.

In the functional food composition for preventing or alleviating symptoms of dementia according to the present invention, the slug blood lymph may be a supernatant obtained by puncturing slugs with a needle or freezing and thawing slugs, then mounting them in a centrifuge and centrifuging. have.

In the functional food composition for preventing or alleviating symptoms of dementia according to the present invention, the fermented slugs or pulverized slugs are put in water and Bacillus subtilis var. It may be fermented by inoculating any one or more strains selected from the group consisting of natto strains, Bacillus subtilis strains and Aspergillus kawachii strains.

The composition as described above according to the present invention may further comprise a chicory root extract.

The composition as described above according to the present invention

any one or more B vitamins selected from the group consisting of vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin B9, and vitamin B12;

vitamin C;

vitamin D;

zinc oxide;

plant lactic acid bacteria;

chicory root extract;

pig placenta extract; and

Acai berry (Acaiberry), strawberry (Strawberry), cranberry (Cranberry), raspberry (Rasberry), blackcurrant (Blackcurrant), blackberry (Blackberry) and any one berry selected from the group consisting of blueberry (Blueberry); cast

may include more.

The composition as described above according to the present invention

Evening primrose oil, borage oil, aloe vera, squalene, lycopene, avocado oil, fucoidan, seokgok, pineberry (also called white strawberry, nucleclavone) and green apple polyphenols can do.

In the composition as described above according to the present invention, the dementia may be Alzheimer's dementia or vascular dementia.

The composition according to the present invention increases spatial working memory, increases visual recognition memory, increases associative learning ability, improves hippocampal cholinergic nervous system function, suppresses Iba-1-IR positive response of microglia and amyloid in Alzheimer's model animals It has been shown to have an excellent effect of inhibiting the formation of plaque, so it is very useful for the prevention, alleviation and treatment of Alzheimer's, and it has a protective effect on brain damaged tissue caused by cerebral ischemia, so it can be used for the prevention and treatment of vascular dementia. .

Therefore, the composition of the present invention can be usefully used as a pharmaceutical composition or a health functional food composition for preventing or treating dementia caused by degenerative brain lesions, such as Alzheimer's dementia and vascular dementia.

1 and 2 are test results for the water-soluble peptide powder and fatty acid oil prepared according to the present invention.
3 is a graph showing the evaluation results of the control group, the composition 1 treatment group, the composition 2 treatment group, and the composition 3 treatment group in the Y-maze test of Alzheimer's disease model animals.
4 is a graph showing the evaluation results of the control group, the composition 1 treatment group, the composition 2 treatment group and the composition 3 treatment group in the new body recognition test of the Alzheimer's disease model animal.
5 is a graph showing the evaluation results of the control group, the composition 1 treatment group, the composition 2 treatment group and the composition 3 treatment group in the passive avoidance test of Alzheimer's disease model animals.
6 is a graph showing the measurement results of choline acetyltransferase activity (ChAT activity) in the hippocampus and cerebral cortex (Cortex) of the control group, the composition 1 treatment group, the composition 2 treatment group and the composition 3 treatment group.
7 is a graph showing the measurement results of acetylcholine levels (Achlevel) in the hippocampus and cortex of the control group, the composition 1 treatment group, the composition 2 treatment group and the composition 3 treatment group.
8 is a graph showing the measurement results of acetylcholinease activity (AchE activity) in the hippocampus and cortex of the control group, the composition 1 treatment group, the composition 2 treatment group and the composition 3 treatment group.
9 is a view showing the effect of the composition according to the present invention on cerebral ischemia.

Hereinafter, the present invention will be described in detail.

The present invention provides a composition for preventing or treating dementia caused by degenerative brain lesions, such as Alzheimer's dementia and vascular dementia, comprising as an active ingredient any one or more selected from the group consisting of slug dry powder, slug blood lymph, and slug fermented broth. provides

The composition according to the present invention increases spatial working memory, increases visual recognition memory, increases associative learning ability, improves hippocampal cholinergic nervous system function, suppresses Iba-1-IR positive response of microglia and amyloid in Alzheimer's model animals It has been shown to have an excellent effect of inhibiting the formation of plaque, so it is very useful for the prevention, alleviation and treatment of Alzheimer's, and it has a protective effect on brain damaged tissue caused by cerebral ischemia, so it can be used for the prevention and treatment of vascular dementia. .

The slug used in the present invention has been used as a medicine for various diseases from oriental medicine for a long time, and is now widely bred in farms and used in oriental medicine or folk remedies. brevitarsis) larvae.

The general component of such slugs is very high about 58% of protein, and also contains a large amount of unsaturated fatty acids. In particular, oleic acid, which is known for its blood pressure lowering effect, accounts for 60% of the total fatty acids, and among minerals, phosphorus, potassium, and vitamins. Silver contains B3 and B9, which has the effect of removing toxins and smoothing blood circulation. Histidine, an essential amino acid for infancy that relieves severe allergy and helps blood formation, helps improve cognitive ability and improves memory. It contains a large amount of glutamic acid and proline, which helps to form cartilage by helping to form collagen.

In addition, slugs are a herbal medicine used as a treatment for liver disease in the private sector, and the liver protection effect of slugs has been scientifically verified in Korea. GOT, GPT, bile acid, and bilirubin levels were investigated for the hepatoprotective effect of Slugfish extract in acute hepatitis induced by carbon tetrachloride. It has been shown to inhibit liver fibrosis in mice with liver cirrhosis, and is expected to be effective as a therapeutic agent.

Such slugs can be used in the composition according to the present invention in powder form, and the powder manufacturing method can be used without any particular limitation as long as it is widely known in the art to which the present invention pertains. For example, a preferred method for manufacturing slug dry powder is Fasting the slugs before manufacturing, preferably for about 4 days to completely remove the wastes remaining in the intestines of the slugs. It is manufactured by a method of drying at 60° C. (hot air drying, drying by a heater, freeze drying are all possible) and manufacturing a powder.

In the present invention, slug blood lymph collected from slugs can be used, and the blood lymph collecting method can be used without particular limitation as long as it is widely known in the art to which the present invention pertains. After freezing and thawing, it is installed in a centrifuge, and after centrifugation, the supernatant is taken to collect the blood lymph from the slugs.

In addition, in the present invention, liquid hemolymph can be prepared and used as a powder. In this case, there are various methods, but the present invention includes the step of preparing a hemolymph powder by freeze-drying the collected hemolymph to produce a powder, which is freeze-dried. This is because when a porous amorphous powder is prepared and dissolved again in a liquid phase, it can be easily dissolved, and it can be used for various purposes by being prepared as a powder having an appropriate volume. Here, the freeze-drying method can be used without particular limitation as long as it is widely known in the art to which the present invention pertains.

Another use form of slugs applicable in the present invention is to put slugs or pulverized slugs in water and Bacillus subtilis var. natto strain, Bacillus subtilis strain and Aspergillus kawachii strain is to use any one or more strains selected from the group consisting of inoculated and fermented fermentation broth.

The above-mentioned fermentation broth consists of an oil phase in the upper layer containing fatty acid oil and an aqueous phase in the lower layer containing water-soluble peptides, which are used together in the present invention, and may be used separately or by adjusting the amount if necessary. .

The slugs used in the fermentation can be used without any particular limitation, whether they are live, dead or dry (the use of water is to sufficiently moisten the slugs so that the fermentation can be performed efficiently, and the amount of water is sufficient for the slugs to You can put it so that it can be locked, and there is no special limitation.

The fermentation temperature for the fermentation may be any suitable temperature to proceed with the fermentation, preferably, the fermentation is performed at room temperature, and the fermentation time is not particularly limited, but is about 5 to 50 hours. Since the fermentation in the present invention can be over-fermented, the inoculation amount of the strain may be inoculated with a sufficient amount to be fermented, but in consideration of efficiency, it is preferable to set it to about 2 to 15% by weight relative to the weight of the used slugs.

When the fermentation according to the present invention proceeds, the oil phase gradually elutes and separates toward the upper layer as the fermentation proceeds, and the lower layer undergoes fermentation of the slugs, disappears and dissolves in the aqueous phase. Therefore, the end of fermentation can be done until the time when the shape of the slugs disappears. In the present invention, as a fermentation strain, Bacillus subtilis var. One or more strains selected from the group consisting of natto strains, Bacillus subtilis strains and Aspergillus kawachii strains were selected. As a result of testing with various strains, the strain most suitable for the purpose of the present invention was selected.

The fatty acid oil and water-soluble peptide prepared as described above are used as active ingredients in pharmaceuticals, health foods, and cosmetic compositions having effects such as fatigue recovery, blood sugar strengthening, anti-dementia, anti-diabetes, antioxidant, liver function improvement, and anti-aging. Very useful.

In addition, in the conventional solvent extraction, it is difficult to completely remove the solvent (residual solvent residual) during extraction using a solvent, and rancidity (peroxide value, free fatty acid increase) due to high-temperature distillation treatment progresses, which leads to deterioration of quality, and also the conventional supercritical extraction Silver extraction rate is low and production cost is very high, making it difficult to commercialize economically, but fermentation extraction according to the present invention does not contain residual solvents, has low peroxide and acid values of physiologically active substances due to low-temperature treatment, and toxic substances from fermentation has the effect of removing

The water-soluble peptide powder and fatty acid oil prepared according to the present invention were tested and the results are attached to Figs. 1 and 2, and the superiority of the present invention can be confirmed by looking at the attached Figs. There are 11 non-essential amino acids as well as essential amino acids such as threonine, tryptophan, valine, phenylalanine, tyrosine, histidine, isoleucine, leucine, lysine, methionine, and cystine, and a natural antibiotic called protecin. Indole alkaloid, a substance that improves blood circulation, relieves eohyeol, such as stroke, dementia, hyperlipidemia, and cholesterol reduction. diabetes treatment. Contains substances showing various effects such as liver function improvement, anticancer, anti-obesity, sarcopenia, myasthenia gravis

In addition, the composition according to the present invention may further include chicory root extract.

In another embodiment, the composition according to the present invention comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin, nicotinamide), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine, pyridoxal, pyridoxamine). ), vitamin B7 (biotin), vitamin B9 (folic acid, folic acid) and vitamin B12 (cobalamin) any one or more vitamin B selected from the group;

vitamin C;

vitamin D;

zinc oxide;

plant lactic acid bacteria;

chicory root extract;

pig placenta extract; and

Acai berry (Acaiberry), strawberry (Strawberry), cranberry (Cranberry), raspberry (Rasberry), blackcurrant (Blackcurrant), blackberry (Blackberry) and any one berry selected from the group consisting of blueberry (Blueberry); cast

may include more.

The root chicory is a kind of Asteraceae, and the main components are inulin, sucrose, cellulose, protein, ash, etc. In Europe, the coarse roots are dried and powdered to be used as a coffee substitute or to reduce the color and bitter taste of coffee. It is also used as an additive for thickening, and the root is used as a folk medicine for diuresis, intestinal tract, dry stomach and purifying blood.

The pig placenta extract is an organ that connects the pups and the mother's uterus, and for the growth of the fetus, such as the function of supplying oxygen and various nutrients necessary for the growth of the pups, as well as the synthesis of factors necessary for the generation of hormones and immunity enhancement necessary for the pups. It is responsible for various functions, and when the offspring are born, the placenta fulfills its functions and is excreted from the mother. This placenta extract contains abundant active ingredients such as various amino acids, active peptides, vitamins, minerals, enzymes and various growth factors. Amino acids present in large amounts in placental extracts are the source of life and have various physiological functions as tissue formation and in vivo chemical reaction regulators. is an important factor in cell formation. Recently, various bio-researches have revealed that it has a wide range of functions, such as antioxidant, anti-inflammatory action, wound healing effect, beauty, fatigue recovery, immune enhancement, constitution improvement, and hematopoietic action.

The vitamin B complex (-複合体, English: vitamin B complex) or vitamin B group (- 群) are water-soluble vitamins that play an important role in cellular metabolism. B vitamins were once known as a single vitamin, but later research has shown that the B vitamins are chemically distinct vitamins that often coexist in the same food. Typically, supplements contain all eight vitamins called the vitamin B complex. Individual B vitamin supplements are called by specific names for each vitamin.

Vitamin B1 (thiamine)

Vitamin B2 (riboflavin)

Vitamin B3 (niacin, nicotinamide)

Vitamin B5 (pantothenic acid)

Vitamin B6 (pyridoxine, pyridoxal, pyridoxamine)

Vitamin B7 (biotin) (also known as vitamin H)

Vitamin B9 (folic acid, folic acid) (also called vitamin M)

Vitamin B12 (Cobalamin)

The present invention may include all in any one or more of these vitamin B complexes, and the content is not particularly limited, and the effect of vitamin B is to strengthen the immune system, strengthen the nervous system, reduce the risk of pancreatic cancer, skin color and Maintaining muscle health and promoting metabolism.

The vitamin D is one of the fat-soluble vitamins that play an important role in the metabolism of calcium and phosphorus. It is essential for the growth of organisms, particularly calcium metabolism, which is involved in the development of bones. Most vitamin D is produced by sunlight, and not much vitamin D comes from food. Your body needs enough vitamin D to keep your bones strong.

The purpose of administering the zinc oxide is to supply zinc. Zinc is an important substance constituting cells in the human body, and if it is insufficient, growth and development are disturbed.

The plant lactic acid bacteria refers to lactic acid bacteria that reproduce in plant foods such as kimchi, soy sauce, and fruits, and is a concept in contrast to animal lactic acid bacteria because they reproduce in animal foods such as milk and yogurt. In the meantime, many efforts have been made, such as encapsulating lactic acid bacteria in capsules to increase the survival rate of animal lactic acid bacteria, but no great effect has been achieved. It shows the characteristics of not dying easily. Examples thereof include Lactobacillus plantarum, Lactobacillus reuteri, Bifidobacterium bifiderm, and Bifidobacterium breve derived from kimchi.

The berry powder is acai berry (Acaiberry), strawberry (Strawberry), cranberry (Cranberry), raspberry (Rasberry), blackcurrant (Blackcurrant), blackberry (Blackberry), blueberry (Blueberry) in at least one of seven berries It means a concentrated powder prepared by using all seven.

The berries are rich in vitamin C and have a good balance between sour and sweet, so they are mostly used for food, and some jams. It is used as a raw material for jelly, ice cream, and alcoholic beverages. Berries have different content depending on the type, but generally contain a lot of organic acids, so they have a sour taste and a lot of sugar. It contains various antioxidants such as flavonols. Here, the polyphenol material has an anti-oxidation function, that is, an antioxidant function. The reason why polyphenols have recently been attracting attention is that this function is expected to contribute to health maintenance and disease prevention by acting as an antioxidant in the living body. In addition, polyphenols prevent cholesterol from being absorbed into the digestive tract, thereby lowering the level of cholesterol in the blood.

In addition, all of the red and purple anthocyanin-based pigments of berries are polyphenol compounds. As for polyphenol substances, a substance in which one of the hydrogens of the benzene ring (C6H6) is substituted with a hydroxyl group (OH) is called phenol. do. Compounds having such a structure mainly exist in nature. Berries are known to play an important role in producing antioxidant, anti-inflammatory, and anti-cancer properties of berries, such as their unique color, polyphenols, or the most special anthocyanins. In particular, berries contain anthocyanins [cyanidin 3-sambubioside, cyanidin 3-glucoside, and cyanidin 3-xylosylrutinoside. ), cyanidin 3-rutinoside and pelargonidin 3-rutinoside, flavonoids [flavonols and flavanols, tannins] (tanins) [proanthocyanidins, ellagitannins and gallotannins], stillbenoids resveratrol and phenolic acids and lignans [Boivin D, et al Anticancer Res 27: 937-948 (2007)] Phenolic compounds derived from natural products and their oxides are components that contribute to the color and taste of foods or beverages using natural products. Recently, various physiological activities such as antioxidant, antimutagenic, anticancer and antihypertensive effects have been revealed. (Cliffe et al, J Agric Food Chem, 42(8), 1824-1828,(1994), Cook and Samman, NutrBiochem) , 7, 66-76 (1996), Bocco et al, J Agric Food Chem, 46 (6), 2123-2129 (1998))

In addition, vitamin C, which is abundantly contained in berries, is known to be essential for various metabolic processes. In other words, vitamin C synthesizes collagen (a protein that makes up skin, tendons, bones, supporting tissues and heals wounds), maintains a constant structural strength of blood vessels, is related to the metabolism of specific amino acids, and synthesizes adrenal hormones. and liberate. Vitamin C also boosts the body's immunity to disease. However, detailed information about each function of vitamin C is still lacking. The daily requirement of vitamin C is 70 mg for an adult male, which is somewhat higher than other vitamins, and is contained in citrus fruits and fresh vegetables. Vitamin C is difficult to store because it is easily destroyed when it reacts with oxygen in neutral or alkaline solutions or at high temperatures. Vitamin C is also used to keep fruits from turning brown.

The powder in the present invention includes all of the powder prepared by drying itself (hot air drying, freeze-drying) and pulverizing the powder or the extract extracted using various extraction solvents to concentration and drying, as the extraction solvent, purified water or ethanol It is preferable to use

The composition according to the present invention may contain various components that can help prevent or treat dementia caused by degenerative brain lesions such as Alzheimer's dementia and vascular dementia, for example, evening primrose oil, borage oil, aloe vera, There are squalene, lycopene, avocado oil, fucoidan, seokgok, pineberry (also called white strawberry, nucleoclavone), green apple polyphenol, and the like.

The evening primrose oil is a vegetable oil extracted by pressing the seeds of evening primrose. It has excellent skin moisturizing and regeneration effects and is effective in relieving premenstrual syndrome, menstrual pain, and menopausal symptoms. It has excellent skin moisturizing and regenerative effects, and helps to relieve premenstrual syndrome and menopausal symptoms.

The aloe vera is a perennial plant of the lily family that is native to Africa. Native to the Mediterranean region and Africa, the clear gel-type sap that comes out when the leaves are cut is effective in treating burns and arthritis. It is contained in vegetable oils. It is particularly abundant in deep-sea shark liver oil, and it is also contained in olive oil, palm oil, wheat germ oil, etc. In the human body, it is synthesized from acetyl coenzyme A through mevalonic acid, cholesterol, reproductive hormones, vitamin D, and bile acids. It is known to be used in production.

The lycopene is a phytochemical and is abundantly contained in fruits having a red color such as tomatoes (tomatoes, watermelons, persimmons, red grapes, pomegranates, grapefruit, and guava). Although it is not converted into vitamin A in the body like beta-carotene, it has a stronger antioxidant action than beta-carotene, and has anti-aging, anti-cancer effects (prostate cancer), cardiovascular disease prevention and blood sugar lowering effects. In particular, it strongly inhibits IGF-1 (insulin like growth factors) factor, a major regulatory factor that promotes cancer cell growth, and stimulates protein 43 enzyme to express the intercellular communication device, and the expression of the intercellular communication device suppresses cancer is closely related to

The avocado oil has a very high monounsaturated fatty acid content and is known as a health food. It has a very high combustion point, so it can be cooked even at very high temperatures, so it is extremely useful for cooking. It is one of the most attractive cooking oils, with its thick, velvety-soft texture and often a fantastic dark green hue.

The fucoidan gives flexibility to brown algae so that the algae can be protected from the violent tidal flow. Fucoidan extracted from brown algae has an average molecular weight of 20 kDa, and a basic sugar called fucose and a sulfate group are combined. There are two types: F-fucoidan, which is generated from sulfated fucoidan, and U-fucoidan, which contains about 20% glucuronic acid. It is known to be used as a basic raw material for functional foods, dietary supplements, and additives. Fucoidan helps excretion of cholesterol, lowers blood cholesterol levels, prevents vascular diseases, and prevents obesity from developing into adult diseases.

The above-mentioned Seokgok is a medicinal material made from the above-ground part of Dendrobium nobile Lindley (金釵石斛) of the orchid family or a closely related plant to replenish the essence, lower the heat, and nourish the stomach. , used for thirst, dry mouth, hard stool, loss of vision due to lack of adultery, and back pain.

The pineberry is a strawberry with red seeds in white or light pink flesh. Also called ‘pineapple strawberry (ananaserdbeere)’, it is smaller in size than normal red strawberries, but has a high sugar content and a scent similar to pineapple. In addition, it is reported that the green apple polyphenol has a high antioxidant ability to protect DNA or cellular proteins and enzymes damaged by exposure to free radicals, thereby lowering the risk of various diseases. In addition, polyphenols are known to have anti-cancer properties and prevent heart disease.

The compositions of the present invention may include an acceptable carrier.

In the present invention, the term "acceptable carrier" may mean a carrier, excipient or diluent that does not inhibit the biological activity and properties of the injected compound without stimulating the organism, and specifically, a non-naturally occurring carrier (non-naturally occurring carrier) ) can be The type of carrier usable in the present invention is not particularly limited, and any carrier commonly used in the art and pharmaceutically acceptable may be used.

The composition may be administered in an effective amount. The "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level depends on the subject type and severity, age, sex, activity of the drug, and the drug. Sensitivity to, administration time, administration route and excretion rate, duration of treatment, factors including concomitant drugs, and other factors well known in the medical field.

In the present invention, the term "food" refers to meat, sausage, bread, chocolate, candy, stacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, tea, drinks, There are alcoholic beverages, vitamin complexes, health functional foods, and health foods, and includes all foods in the ordinary sense.

The functional food is the same term as food for special health use, FoSHU. means food. Here, "function (sex)" means to obtain a useful effect for health purposes such as regulating nutrients or physiological action with respect to the structure and function of the human body. The food of the present invention can be prepared by a method commonly used in the art, and at the time of manufacture, it can be prepared by adding raw materials and components commonly added in the art.

In addition. The formulation of the food may also be prepared without limitation as long as it is a formulation recognized as a food. The composition for food of the present invention can be prepared in various forms, and unlike general drugs, it has the advantage that there are no side effects that may occur when taking the drug for a long period of time using food as a raw material, and has excellent portability, and the present invention Foods of can be taken as a supplement to alleviate Alzheimer's.

Hereinafter, the present invention will be described in more detail through examples. However, the following examples are intended to illustrate the present invention, and the scope of the present invention is not limited thereto.

< Example 1: Anti-Alzheimer's Effect Test>

1. Preparation of Animals

All animals were treated in accordance with the NIH Guide for the Welfare and Use of Test Animals (NIH Publication No 85-23, 1985; wwwdelsnasedu/ila). The present invention was carried out in accordance with ILAR (Institute for Laboratory Animal Research) guidelines for the welfare and use of test animals.

6-month-old APP/PS1 (amyloid precursor protein/presenilin-1, APPswe/PS1dE9) double transgenic mice (The Jackson Laboratory, Bar Harbor, MA, USA) were used as Alzheimer's model animals, 12:12h : The arm cycle was maintained and ad libitum was carried out.

2. Composition treatment

Each of the following treatment compositions was administered at 50 mg/kg to test animals for 90 days, and behavioral evaluation (Y-maze test, body recognition test, passive avoidance test) was performed on days 60 to 63 and 90 to 93 days. .

The test was carried out by classifying it into 4 groups: Composition 1 treatment group, Composition 2 treatment group, Composition 3 treatment group, and control group (No treatment), and each group was n=6.

Treatment composition 1: composition consisting of slug powder

Treatment composition 2: A composition in a weight ratio of 1:1 consisting of slug powder and chicory root extract powder

Treatment composition 3: slug powder, vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin, nicotinamide), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine, pyridoxal, pyridoxamine), vitamin B7 (biotin), vitamin B9 (folic acid, folic acid). vitamin B12 (cobalamin), zinc oxide; Plant Lactobacillus Plantarum, Chicory Root Extract, Vitamin C, Vitamin D, Pig Placenta Extract, Acaiberry, Strawberry, Cranberry, Raspberry, Blackcurrant , blackberry (Blackberry) and blueberry (Blueberry), weight ratio slug powder 20; Chicory Root Extract Powder 20; the rest of the composition of 0.1 each

As the slug powder, washed well in water and dried slugs were added, and as a fermentation strain, Bacillus subtilis var. After adding natto in an amount of about 3% by weight based on the weight of the dried slugs and maintaining it at room temperature, fermentation was carried out for 20 hours to separate the oil phase of the upper layer and the aqueous phase of the lower layer, and then the separated aqueous phase was filtered under reduced pressure using a 1㎛ filter. The filtered aqueous phase was sterilized at 121° C. for 30 minutes to remove microorganisms, and the solution was freeze-dried to prepare and use a water-soluble slug peptide powder.

3. anti-alzheimer's Efficacy evaluation

(1) Y-maze test (Y-maze)

The Y-shaped maze test was performed as described in J Alzheimers Dis (31, 207-223). The Y-maze consists of a Y-shaped arm and a black plastic box with a length of 25cm X 25cm X 14cm.

Place the mouse on the tip of one arm and allow it to move freely between arms for 8 min. The number of times the mouse enters each arm is recorded with a video camera. The evaluation index of the alternative behavior (Alternation behavior) was compared with the control group by obtaining 1 point in the case of entering all three cancers. The replacement score of the mouse is converted to 100% by dividing the score obtained by the actual mouse by the possible replacement score.

(2) new body Novel Object Recognition

The new body recognition test was performed as described in the prior literature [Learn Mem (14, 117-125)]. On the first day, acclimatize the mice by placing them in a box of 40 cm X 40 cm X 30 cm and allowing them to move freely for 10 minutes. On day 2, place two objects in a box and record the reaction time for each object. After 24 hours, one of the two objects is replaced with a new object (novel object) and the reaction time is recorded.

(3) Passive Avoidance test

The passive avoidance test was performed using the Gemini Avoidance System (SanDiego Instrument, San Diego, CA) as described in the prior literature [Behav Brain Res (155, 185-196)]. The system consists of two spaces in which a shock generator is installed on the floor, and there is a guillotine door between the two spaces.

In the learning phase (Acquisition trial), the mouse is put in a start chamber and then acclimatized for 20 seconds, and after 20 seconds, the light in the space in which the mouse is put is turned on and the guillotine door in the middle is opened. As soon as the mouse enters the opposite space where the light is not turned on, the guillotine door closes and an electric shock (03 mA, 3s, 1 time) is given.

In a retention trial after 24 hours, the mice were placed back in the start chamber, turned on, and the step-through latency was recorded (up to 300 seconds).

(4) Choline acetyltransferase activation( ChAT activity), acetylcholine levels ( Ach level) and acetylcholinease activity ( AchE activity) measurement

24 hours after the manual avoidance test, the hippocampus and cortex were cut out, crushed with an ultrasonic tissue grinder (Bronson Sonic, NY), centrifuged at 10,000 g, 4 ° C for 20 minutes, and the supernatant was taken and acetylcholine (acetylcholine) was removed. ) concentration, acetyl cholinesterase, and choline acetyltransferase activity were measured.

ACh levels and AChE activity in hippocampal and cortical tissues were measured using a kit (Amplex® Red Acetylcholine/ Acetylcholinesterase Assay Kit, Molecular Probes, Inc, Eugene, KOR) according to the manufacturer's protocol.

ChAT activity was determined by Mehta et al. [Mehta H, Haobam R, Usha R, Mohanakumar KP Evidence for the involvement of central serotonergic mechanism in cholinergic tremor induced by tacrine in Balb/c mice Behav Brain Res 20.05; 163: 227-236]. Namely, 0.5M sodium phosphate buffer (pH 7.2), acetyl-CoA (6.2 mM), choline chloride (1M), neostigmine sulfate (0.76 mM), NaCl (3M) and 25 μl of EDTA (11 mM) solutions were each taken, and the volume was adjusted to 400 μl using distilled water. This solution was preincubated at 37°C for 5 minutes, and then 100 μl of the sample was added and incubated at 37°C for 20 minutes.

After boiling the sample for 2 minutes to terminate the reaction, 1 ml of distilled water was added, centrifuged to remove denatured protein, and 1 ml of the supernatant was diluted with 30 μl of dithiopyridine (4,4′-dithiopyridine, 10 mM). It was placed in a test tube and the absorbance was measured at 324 nm after 15 minutes.

ChAT activity was expressed as coenzyme nmol/hr·g protein. Protein concentration was measured using a BCA protein assay reagent (Pierce, Rockford, IL, USA) according to the manufacturer's protocol.

4. Test results

(1) Y-maze test

The test results are shown in FIG. 3 . Referring to FIG. 3 , administration of the composition of the present invention in mice significantly increased the space change behavior compared to the control group (50 mg/kg, P<0.05).

The composition of the present invention showed a more remarkable increase trend as the administration period was increased, and in particular, compositions 2 and 3 exhibited better effects than composition 1.

(2) new body cognitive test

The test results are shown in FIG. 4 , which shows that administration of the composition of the present invention in mice significantly increased the search behavior for new objects in the new object recognition test compared to the control group (P<0.05), which It means an increase in visual recognition memory.

The composition of the present invention showed a more remarkable increase trend as the administration period was increased, and in particular, compositions 2 and 3 exhibited better effects than composition 1.

(3) Passive evasion test

The test results are shown in FIG. 5, and the administration of the composition of the present invention in mice significantly increased the stepthrough latency to the black room in the passive avoidance test compared to the control group (P<0.05), which was associated with It means an increase in associative learning.

The composition of the present invention showed a more remarkable increase trend as the administration period was increased, and in particular, compositions 2 and 3 exhibited better effects than composition 1.

(4) Choline acetyltransferase Determination of activity, acetylcholine levels and acetylcholinease activity

The test results are shown in Figs. 6 to 8, and the administration of the composition of the present invention in mice was compared to the control group at the concentration of acetylcholine in the hippocampus tissue (P<0.05) and the acetylcholine synthetase choline. The activity of acetyltransferase was significantly increased (P<0.05), and the activity of acetylcholinesterase, an acetylcholinesterase, was significantly decreased (P<0.05), indicating that the cholinergic nervous system function of the hippocampus was increased. it means.

The above results indicate that administration of the composition of the present invention has a significant pharmacological effect on improving hippocampal cholinergic nervous system function, and in particular, compositions 2 and 3 exhibited better effects than composition 1.

< Example 2: in cerebral ischemia Protective effect of brain damaged tissue caused by

To observe the protective effect of Ganoderma extract against brain tissue infarction induced by cerebral ischemia, an animal model of cerebral ischemia was created by occluding middle coronary artery occlusion (MCAO) in mice (Longa et al, 1986).

Male rats (Sprague-Dawley) weighing 250-300 g were used, and they were allowed to freely drink water and food before and after induction of cerebral ischemia.

After induction of anesthesia by introducing 30~35% of enflurane (Chungwae Pharmaceutical) in the anesthesia chamber, 15~20% of enflurane was introduced as a mask to continue anesthesia during surgery. In order to prevent body temperature drop, the body temperature was maintained at 37±0.5° C. using an electric blanket during surgery. After making a 1 cm incision in the neck along the midline of the neck, the right common carotid artery was carefully separated from the vagus nerve and exposed. The external carotid artery and the internal carotid artery were separated from the surrounding nerves from the common carotid artery, and a thread was previously loosely hung on the dissected common carotid artery, external carotid artery, and internal carotid artery. The common carotid artery and the external carotid artery are ligated by tying a tendon thread to the common carotid artery and the external carotid artery, a hole is made at the origin of the internal carotid artery with a needle, and a 17mm-long probe is pushed through the incision toward the internal carotid artery to close the middle cerebral artery. , ischemia was induced by fixing the probe by tying a thread hung on the internal carotid artery. At this time, the probe is used as a stopper by heating one end of a nylon surgical thread near the pharynx so that the diameter of the tip becomes 03mm, cutting it to about 17mm in length, and then using a hardener (Optosil). , Bayer Dental) added silicone (Xantopren, Bayer Dental) was used. The surgical site was sutured and placed in another cage until awakening from anesthesia. When a certain period of time (about 30 minutes) has elapsed after inducing cerebral ischemia, a neurological deficit was confirmed. Neurological deficits were observed in white rats with left hemiparesis when the tail was fully lifted in the air, and circling to the left when the tail was lifted up or spontaneously (Bederson et al, 1986). )

In this test, after intraperitoneal pre-treatment with Composition 2 (0.5 mg/kg, 2.0 mg/kg, 10 mg/kg), the middle cerebral artery was occluded 30 minutes later to induce cerebral ischemia for 9 hours, and then the single head The brain was quickly removed. Using a brain matrix (Neurotec Korea), 0.9 in the third piece (5-7 mm) of fresh brain coronal slices continuously separated 2 mm thick from the point 1 mm from the frontal pole. After adding 2% TTC (2,3,5-triphenyltetrazolium chloride) solution prepared with % physiological saline, and staining at 37° C. for 30 minutes, the degree of brain damage was measured, and the results are shown in FIG. 9 .

As shown in FIG. 9 , it can be seen that the range of damage (the area that appears white) in the cerebral cortex and the striatum induced by ischemia for 9 hours is reduced by administration of the composition 2 according to the present invention.

Claims (7)

A functional food composition for preventing or alleviating symptoms of dementia comprising, as an active ingredient, any one or more selected from the group consisting of slug dry powder, slug blood lymph, and slug fermented broth.
The functional for prevention or symptom relief of dementia according to claim 1, wherein the slug blood lymph is a supernatant obtained by puncturing slugs with a needle or freezing and thawing slugs, then installing them in a centrifuge and centrifuging them. food composition.
The method according to claim 1 or 2, wherein the slug fermentation broth is prepared by adding slugs or pulverized slugs to water, and Bacillus subtilis var. A functional food composition for preventing or alleviating symptoms of dementia, characterized in that it is fermented by inoculating any one or more strains selected from the group consisting of natto strains, Bacillus subtilis strains and Aspergillus kawachii strains.
The functional food composition for preventing or alleviating symptoms of dementia according to claim 1, further comprising chicory root extract.
The method of claim 1,
any one or more B vitamins selected from the group consisting of vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin B9, and vitamin B12;
vitamin C;
vitamin D;
zinc oxide;
plant lactic acid bacteria;
chicory root extract;
pig placenta extract; and
Acai berry (Acaiberry), strawberry (Strawberry), cranberry (Cranberry), raspberry (Rasberry), blackcurrant (Blackcurrant), blackberry (Blackberry) and any one berry selected from the group consisting of blueberry (Blueberry); cast
Functional food composition for preventing or alleviating symptoms of dementia, characterized in that it further comprises.
Section 1. The method according to any one of claims 4 and 5, wherein evening primrose oil, borage oil, aloe vera, squalene, lycopene, avocado oil, fucoidan, seokgok, pineberry (also called white strawberry, nucleoclavone) and green apple Functional food composition for preventing or alleviating symptoms of dementia, characterized in that it further comprises any one or more selected from the group consisting of polyphenols.
The functional food composition for preventing or alleviating symptoms of dementia according to claim 1, wherein the dementia is Alzheimer's dementia or vascular dementia.

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