JP2007145840A - Composition for preventing and treating recognition functional disorder, containing naphthoquinone-based compound - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a pharmaceutical composition useful for the prevention and treatment of recognition functional disorder by having a recognition functional disorder-improving effect such as the suppression of aggregation of beta-amyloid, known as a cause of Alzheimer's disease and the inhibition of cell toxicity caused by the beta-amyloid, and a health functional food. <P>SOLUTION: This pharmaceutical composition is provided by containing a naphthoquinone compound, and especially containing the naphthoquinone compound selected from naturally existing juglone, 5,8-hydroxy-1,4-naphthoquinone and 1,2-naphthoquinone as an active ingredient. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a composition for preventing and treating cognitive dysfunction comprising a naphthoquinone compound present in a natural plant.

  The central nervous system, consisting of the brain and spinal cord, is the central center for managing life phenomena, from sensory and (in) voluntary movements to thinking, memory, emotion, language, etc. It is an indispensable organ that summarizes all functions of the human body. Therefore, rapid neuronal cell death caused by stroke or trauma, and slow neuronal cell death that induces degenerative diseases of the central nervous system such as senile dementia and Parkinson's disease represented by Alzheimer's disease, etc. In all cases, it will immediately lead to irreversible dysfunction of the neural network and ultimately to permanent loss of its human function. Senile dementia, typified by Alzheimer's disease, has properties that increase in proportion to the extension of the average life expectancy of humans and the modernization of medical welfare facilities. According to a statistical survey by the Institute of Insurance Society, Japan's elderly population exceeded 7% in 2000 and entered an aging society, reaching 3.97 million in 2003. Is expected to reach 8.3%, reaching 14.4% in 2019 and entering a fully aging society. The elderly who have one or more types of chronic diseases in the elderly population over 65 years old have reached, and in particular, the prevalence of dementia in elderly people over 65 years old is estimated to be 8.2%. In Western society, Alzheimer's disease has occurred in about 10% of the population over the age of 65 and about 40-50% of the population over the age of 80. In the United States, there are already over 5 million patients. It is estimated that the expenditure of medical expenses caused by In Japan, it has been found that about 200,000 people or more are demented patients. In the case of the United States, it is estimated that it will increase to double the current scale by 2030 and increase by more than 350% to 20 million by 2050.

  Alzheimer-type senile dementia that begins with cognitive dysfunction is caused by the accumulation of an abnormal protein called `` beta amyloid '' in cranial nerve cells and a lack of cerebral neurotransmitter called acetylcholine. And treatment measures are not clear. Beta amyloid is a major component of plaque, and the phenomenon of plaque accumulation in the brain is one of the typical features of Alzheimer's disease. Therefore, reducing beta amyloid production early in the onset of Alzheimer's disease has a significant effect on delaying the progression of the disease.

  Alzheimer's disease is a degenerative disease that progresses over a long period of time when human nature is destroyed. Therefore, depending on the passive method of accommodating a patient, it cannot endure the socio-economic burden, preventing and treating the cause. An aggressive attempt to develop a drug must be carried out. However, to date, no therapeutic agent capable of treating the underlying cause of Alzheimer's disease has been developed. As a general therapeutic agent, an acetylcholinesterase inhibitor Pfizer Aricept ( Alicept, Exelon from Novartis, and Reminyl from Janssen, and Ebixa from Lundbeck, an antagonist mechanism for the NMDA receptor recently approved by the US FDA. However, in the case of an acetylcholinesterase inhibitor, only the reduced cognitive ability is improved and the underlying cause of Alzheimer's disease cannot be treated. In addition, only in some patients (about 40-50%), it shows a temporary relaxation effect and cannot be sustained for a long time. difficult. In addition, due to the characteristics of the disease, long-term administration is required, and in the case of the above medicines, it has been found as a problem that it has various side effects such as hepatotoxicity, vomiting, and decreased appetite. Yes. Therefore, the development of therapeutic agents that can block the progression of disease has become an urgent issue. For this reason, a large number of multinational pharmaceutical companies have invested enormously in research and development in this field, and in particular, beta amyloid composed of more than 40 amino acids, which is estimated to be the root cause of Alzheimer's disease. The development of beta or gamma secretase inhibitors that reduce the production of is the main type. In Japan, basic research on Alzheimer's disease has been realized to some extent, but the development itself of dementia treatment itself seems to be almost complete. In the case of gamma secretase inhibitors, not only in animal experimental models but also in the results of recent clinical experiments, the prospects are uncertain because they are associated with considerable toxicity. Although the research and development period is relatively short, in the case of beta-secretase, as shown in the results of gene-deficient transgenic animal models, it is a promising target for the development of a safer and more efficient dementia treatment. It can be said that there is. In addition, it is considered that a target targeting a factor involved in the aggregation of beta amyloid is relatively safe. Recently, in the development of new drugs targeting beta amyloid, it has been confirmed that Ensonics in the United States has performed a clinical two-phase on a drug called phenserine, which has a dual function, It is reported that it also has a cholinesterase inhibitory effect (Greig et al., J. Med. Chem. 44, pp. 4062-4071, 2002; Medical News Today, September 4, 2004) Www.medalnewstoday.com; American Alzheimer Association homepage (www.alzform.org/drg/drc).

  Another possible method is the development of a vaccine using beta amyloid (Vaccine). A series of research and clinical results conducted mainly by Elan reports that beta amyloid peptide can be used as a vaccine. Has occurred and is in an interrupted state. Currently, vaccines using various beta amyloid structures are being developed. From the results of animal experiments, it has been found that beta amyloid vaccine reduces the number of senile plaques formed in the brain and improves the cognitive ability of model animals. It is also possible to alleviate Alzheimer by enhancing the activity of brain cells and enhancing the activity of damaged brain neurons and improving cognitive function

  Naphthoquinone is a quinone having a naphthalene ring skeleton and is composed of three isomers of 1,2- (α-), 1,4- (α-) and 2,6- (amphi-). Is present. 1,4-naphthoquinone derivatives are naturally distributed as animal pigments, and 2,6-naphthoquinone is unstable and decomposes immediately in solution. It is irritating to all skins and exists as crystals with a quinone-specific color. 1,2-naphthoquinone is used as a reagent and an intermediate, and 1,4-naphthoquinone is used as a polymerization regulator for rubber and polyester resin, in addition to being used as a raw material for dyes and pharmaceuticals, and as a disinfectant. Has also been used. Quinones are one of a very large group of herbal ingredients and are widely distributed across animals, plants and microorganisms. Anthraquinone (a typical compound is emodin) is the most common, followed by naphthoquinone and benzoquinone. Although these have many components having physiological activity, ubiquinone, which plays an important role in the in vivo electron transport system, vitamin K which shows blood coagulation action, mitomycin which shows anticancer action, and a majesty action Many are important as pharmaceuticals, such as cenoside. In addition, there are many important dyes such as alkannin, alizarin, shikonine (Research trends in domestic bioactive natural products as functional food materials, Hwang Kumhi, Kim Hyungu) , Food Science and Industry, 28 (3), 1995;

  Vitamin K, which is a derivative of naphthoquinone, mainly promotes blood coagulation. As an active substance, many homologues such as vitamin K (pyroquinone), vitamin K (menaquinone), vitamin K (menadione) are isolated or isolated. Synthesizing. Vitamin K promotes the generation of blood coagulation factors such as prothrombin and maintains the blood coagulation function normally, and is also called an anti-hemorrhagic vitamin. In addition, anticancer effects have been reported, and it has been found that 5-hydroxy-2-methoxy-1,4-naphthoquinone has an effect on solid cancer (Korea Patent Publication No. 180791, Konil Pharmaceutical, 6- Substituted-5,8-dioxy-1,4-naphthoquinone derivatives; U.S. Pat. No. 5,696,276 (5,8-Dihydroxynaphthoquinone derivatives)).

  As such efficacy of naphthoquinone becomes clear, application to various diseases has been attempted, but literature on brain disease related research has never been disclosed or published.

  In the present invention, a natural product library was screened for the purpose of isolating substances having therapeutic and preventive effects on cognitive dysfunction by an established screening method. As a result, we observed the excellent inhibitory activity of naphthoquinone compounds on the aggregation of beta amyloid, confirmed a significant inhibitory activity against the cytotoxicity of the aggregated beta amyloid, and at the same time confirmed that it is a safe drug with low cytotoxicity of its own. Confirmed and completed the present invention.

  The present invention provides a composition for preventing and treating cognitive dysfunction comprising a naphthoquinone compound as an active ingredient.

  In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating cognitive dysfunction comprising a naphthoquinone compound as an active ingredient.

  Specifically, juglone represented by the following chemical formulas 1-3, 5,8-hydroxy-1,4-naphthoquinone (5,8-hydroxy-1,4-naphthoquinone), and 1,2-naphthoquinone Provided is a pharmaceutical composition for preventing and treating cognitive dysfunction comprising a naphthoquinone compound selected from (1,2-naphthoquinone) as an active ingredient.

  Said cognitive dysfunction includes Alzheimer's dementia, cerebrovascular dementia, pick disease, Creutzfeldt-jacob disease, dementia due to head injury, or Parkinson's disease, Desirably, it includes Alzheimer's dementia.

(Chemical formula 1) Juglon

(Chemical Formula 2) 5,8-hydroxy-1,4-naphthoquinone

(Chemical Formula 3) 1,2-Naphthoquinone

  The present invention also includes juglone, 5,8-hydroxy-1,4-naphthoquinone (5,8-hydroxy-1,4-naphthoquinone) represented by the above chemical formulas 1 to 3, and 1,2 Provided is a health functional food for preventing and improving cognitive dysfunction comprising, as an active ingredient, a naphthoquinone compound selected from naphthoquinone (1,2-naphthoquinone).

  As a result of investigating the influence of the compound of the present invention on the cognitive dysfunction improving effect, cognition such as inhibiting the aggregation of beta amyloid known as the cause of Alzheimer's disease and inhibiting the cytotoxicity caused by beta amyloid By having a function recovery effect, it was confirmed that the composition was usefully usable as a composition for preventing and treating cognitive impairment.

  The pharmaceutical composition for the prevention and treatment of cognitive dysfunction-related diseases of the present invention comprises 0.02 to 50% by weight of the above compound based on the total weight of the composition.

  Pharmaceutical compositions containing the compounds of the present invention can further include suitable carriers, excipients, and diluents commonly used in the manufacture of pharmaceutical compositions.

  Carriers, excipients, and diluents that can be included in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, zyitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate , Calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.

  The pharmaceutical dosage forms of the compounds of the present invention can be used in the form of their pharmaceutically acceptable salts, as well as in a suitable assembly as well as alone or in combination with other pharmaceutically active compounds. It can also be used.

  The pharmaceutical composition containing the compound according to the present invention is prepared according to the usual methods, such as oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations and suppositories. And carriers, excipients, and diluents that can be used in the form of a sterile injectable solution and can be included in a composition containing a compound are lactose, dextrose, sucrose, sorbitol, mannitol, zyitol, erythritol , Maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and minerals It can be mentioned. In the case of formulating, it is manufactured using a diluent or excipient such as a filler, a bulking agent, a binder, a wetting agent, a disintegrant, and a surfactant that are usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, such solid formulations contain at least one or more excipients in the above extract, for example It is produced by mixing starch, calcium carbonate, sucrose, lactose, gelatin or the like. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Examples of liquid preparations for oral use include suspensions, liquids for internal use, oils, syrups, etc., but besides water and liquid paraffin, which are commonly used simple diluents, various excipients such as Wetting agents, sweeteners, fragrances, preservatives and the like can be included. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, oils, lyophilized formulations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol (polypropylene glycol), polyethylene glycol, vegetable oils such as olive oril, and injectable esters such as ethyl oleate can be used. As a suppository base, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

  The desired dosage of the compound of the present invention varies depending on the condition and weight of the patient, the severity of the disease, the form of the drug, the administration route and the period, but can be appropriately selected by those skilled in the art. However, for desirable effects, the compound of the present invention should be administered at 0.0001 to 100 mg / kg, preferably 0.001 to 10 mg / kg per day. Administration can be performed once a day, or can be divided into several times. The above doses do not limit the scope of the present invention in any way.

  The compounds of the present invention can be administered by various routes to mammals such as mice, mice, domestic animals, humans and the like. Any mode of administration can be envisaged, for example, administered by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dura mater, or intracerebral intravascular injection.

  The present invention provides a health functional food containing the compound of Chemical Formula (1) to Chemical Formula (3) of FIG. 1 showing the preventive effect on a cognitive dysfunction related disease and a food supplement that is foodically acceptable. Examples of foods to which the compound of the present invention can be added include various foods, beverages, gums, teas, vitamin complex agents, and health functional foods.

  It can also be added to foods or beverages for the purpose of preventing cognitive dysfunction-related diseases. At this time, the amount of the compound in the food or beverage is generally 0.01 to 50% by weight, preferably 0.01 to 15% by weight of the whole food weight of the health functional food composition of the present invention. In the case of a health drink composition, it can be added at a ratio of 0.02 to 5 g, preferably 0.3 to 1 g based on 100 ml.

  The health functional food of the present invention includes forms such as tablets, capsules, pills, and liquids.

  The health drink composition of the present invention does not have any special restrictions regarding the further ingredients except that it contains the above-mentioned compound as an essential ingredient in the indicated ratio, like a normal drink. Various flavoring agents or natural carbohydrates can be added as additional components. Examples of the above-mentioned natural carbohydrates are monosaccharides such as disaccharides such as glucose and fructose, polysaccharides such as maltose and sucrose, conventional sugars such as dextrin and cyclodextrin, and zylitol, sorbitol and erythritol. Such as sugar alcohol. As flavoring agents other than those mentioned above, natural flavoring agents (thaumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, asphaltum, etc.) can be advantageously used. The carbohydrate ratio is generally about 1-20 g, preferably about 5-12 g, per 100 ml of the composition of the present invention.

  In addition to the above, the compounds of the present invention include various nutrients, vitamins, minerals (electrolytes), synthetic flavors, flavors such as natural flavors, colorants, and fillers (cheese, chocolate, etc.), pectic acid and Its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonates used in carbonated beverages, and the like can be included. Apart from this, the compounds of the invention can contain natural fruit juices and fruit juice drinks, as well as pulp for the production of vegetable drinks. Such components can be used independently or in combination. The proportion of such additives is not critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

  Hereinafter, the present invention will be described in detail by the following experimental examples.

  However, the following experimental examples are merely illustrative of the present invention, and the contents of the present invention are not limited by the following reference examples and experimental examples.

Example 1. Preparation of compounds
Juglone, 5,8-hydroxy-1,4-naphthoquinone (5,8-hydroxy-1,4-naphthoquinone), and 1,2-naphthoquinone are available from Sigma Chemical Co., Ltd. Co.,: ST. Luis, MO, USA), and the other reagents used were the highest grades available in the market.

(Experimental example 1. Inhibition experiment of beta amyloid aggregation)
Beta amyloid is a major component of plaque, and the phenomenon of plaque accumulation in the brain is one of the typical features of Alzheimer's disease. The aggregation suppression experiment of the naphthoquinone compound of the present invention was performed using beta amyloid 1-42 (BACHEM) which can be purchased in the city. Beta amyloid completely dissolved in DMSO at 250 μM is diluted to 1/10 with PBS on a fluorescent black plate to induce aggregation. Then, the beta amyloid aggregation inhibitory ability of each naphthoquinone compound was compared, and a compound showing an inhibitory effect of 50% or more at 10 μg / ml was selected and added as a sample, and then reacted at room temperature for 1 hour. ThT (Thioflavin T) was diluted in 50 mM glycine buffer, 150 μl was added per well, and the absorbance was measured with a microplate reader (SAFIRE, TECAN) at an excitation wavelength of 450 nm / an emission wavelength of 480 nm.

The ability of juglone to inhibit beta amyloid aggregation was measured at a concentration of 10 μg / ml, and an inhibitory effect of 89.9% was confirmed. When inhibition of 50% or more is shown, the IC ₅₀ value is obtained through an experiment according to concentration, so that aggregation occurs at various concentrations such as 0.05 μg / ml, 0.5 μg / ml, 5 μg / ml, and 50 μg / ml. Inhibitory ability was confirmed. The degree of aggregation suppression by juglone concentration is shown in FIG. 2, and it was confirmed that the IC ₅₀ value was 2.5 μg / ml.

The ability of 5,8-hydroxy-1,4-naphthoquinone (5,8-hydroxy-1,4-naphthoquinone) to inhibit beta amyloid aggregation was measured at a concentration of 10 μg / ml, and an inhibitory effect of 61.3% was confirmed. . By determining the IC ₅₀ value through an experiment for each concentration, the ability to suppress aggregation was confirmed at various concentrations such as 0.05 μg / ml, 0.5 μg / ml, 5 μg / ml, and 50 μg / ml. The degree of aggregation suppression by concentration of 5,8-hydroxy-1,4-naphthoquinone is shown in FIG. 3, and it was confirmed that the IC ₅₀ value was 3.56 μg / ml.

The ability of 1,2-naphthoquinone to inhibit beta amyloid aggregation was measured at a concentration of 10 μg / ml, and an inhibitory effect of 91.3% was confirmed. When inhibition of 50% or more is shown, the IC ₅₀ value is obtained through an experiment according to concentration, thereby aggregating at various concentrations such as 0.05 μg / ml, 0.5 μg / ml, 5 μg / ml, and 50 μg / ml. Inhibitory ability was confirmed. The degree of aggregation suppression by concentration of 1,2-naphthoquinone is shown in FIG. 4, and it was confirmed that the IC ₅₀ value was 1.26 μg / ml.

(Experimental example 2. Experiment of toxicity-inhibiting effect of beta amyloid)
(2-1. Preparation of cells)
HT22, a mouse neuronal cell line, was added to DMEM (Dulbecco's Modified Eagle's Medium, Gibco-BRL) medium with 10% FBS (Fetal Bovine Serum, Hyclone) and 1% Penicillin / Streptomycin (Streptomycin). The cultured medium was used and cultured in an incubator (Forma) at 37 ° C. and 5% CO ₂ . Prior to entering the experiment, HT22 cells were plated in 96-well plates at a density of 5 × 10 ³ cells / well and then cultured in DMEM medium with serum removed for 1 hour before processing the samples.

(2-2. Measurement of cell necrosis suppression degree)
After adding the sample at a concentration of 10 μg / ml and culturing for 1 hour, after treating aggregated beta amyloid 25-35 (US peptide) at a concentration of 25 μM, culturing for 18 hours to induce cell necrosis 15 μl of 5 mg / ml MTT (3- (4,5-dimethyl-2-thiazoline) -2,5-diphenyl-2H-tetrazolium bromide) solution was added per well, and after 4 hours of incubation, 100 μl of lysis buffer (10% SDS, 50% dimethylformamide, pH 4.7) was added and allowed to react overnight. After 18 hours, absorbance was measured at 570 nm / 630 nm using a microplate reader (Sunrise, TECAN) to confirm the inhibitory effect on beta amyloid toxicity (illlardon, F. et al., Brain Research, 706 (1)). , Pp 169-172, 1996), shown in FIG.

  Experimental results have confirmed that 5,8-hydroxy-1,4-naphthoquinone most effectively protects cells from beta amyloid toxicity.

(Experimental example 3. Cytotoxicity measurement)
In order to measure the cytotoxicity of the naphthoquinone-based compound itself and investigate side effects due to toxicity of the sample itself that may occur in the future, a cytotoxicity experiment was performed using the nerve cell line HT22 of Experimental Example 2-1.

  Each sample was processed at a concentration of 10 μg / ml to determine its own toxicity and is shown in FIG. 5,8-Hydroxy-1,4-naphthoquinone has no cytotoxicity, but juglone and 1,2-naphthoquinone showed some cytotoxicity. In the case of juglone, the effects of inhibiting beta amyloid toxicity and cytotoxicity were complementary to each other.

  As a result of the experiment, in naphthoquinone, when 5,8-hydroxy-1,4-naphthoquinone performs two functions of beta amyloid aggregation inhibiting ability and protecting neuronal cells from neuronal necrosis caused by beta amyloid. At the same time, it was confirmed that the substance is safe and has no cytotoxicity.

  Although the formulation example of the pharmaceutical composition containing the compound of this invention is demonstrated, this invention does not intend to limit this but only intends to explain concretely.

(Formulation example 1. Production of powder)
Juglon 20mg
Lactose 100mg
Talc 10mg
The above ingredients are mixed and filled into an airtight package to produce a powder.

(Formulation example 2. Production of tablets)
5,8-hydroxy-1,4-naphthoquinone 10 mg
Corn starch 100mg
Lactose 100mg
Magnesium stearate 2mg
After mixing the above ingredients, tablets are produced by tableting in accordance with a conventional tablet production method.

(Formulation example 3. Production of capsules)
1,2-naphthoquinone 10mg
Crystalline cellulose 3mg
Lactose 14.8mg
Magnesium stearate 0.2mg
According to a usual capsule manufacturing method, the above ingredients are mixed and filled into a gelatin capsule to prepare a capsule.

(Formulation example 4. Production of injection)
Juglon 10mg
Mannitol 180ng
Sterile distilled water for injection 2974mg
Na ₂ HPO ₄ . 12H ₂ O 26mg
Manufacture with the above component content per ampoule (2 ml) according to the usual injection manufacturing method.

(Formulation Example 5. Production of solution)
5,8-hydroxy-1,4-naphthoquinone 20 mg
Isomerized sugar 10g
Mannitol 5g
Purified water Appropriate amount Each component is added and dissolved in purified water according to the normal method for producing liquids, and after adding a proper amount of lemon scent, the above components are mixed, and then purified water is added to adjust the whole to 100 mg. After that, a brown bottle is filled and sterilized to produce a solution.

(Formulation Example 6. Production of health food)
1,2-naphthoquinone 1000mg
Vitamin mixture appropriate amount Vitamin A acetate 70μg
Vitamin E 1.0mg
Vitamin B ₁ 0.13mg
Vitamin B ₂ 0.15mg
Vitamin B ₆ 0.5mg
Vitamin B ₁₂ 0.2μg
Vitamin C 10mg
Biotin 10 μg
Nicotinamide 1.7mg
50 μg of folic acid
Calcium pantothenate 0.5mg
Inorganic mixture Appropriate amount Ferrous sulfate 1.75mg
Zinc oxide 0.82mg
Magnesium carbonate 25.3mg
Primary potassium phosphate 15mg
Dicalcium phosphate 55mg
Potassium citrate 90mg
Calcium carbonate 100mg
Magnesium chloride 24.8mg
The composition ratio of the above-mentioned vitamin and mineral mixture is a composition that is a composition suitable for a health food as a preferred embodiment, but there is no problem even if this blending ratio is arbitrarily changed, and a normal health food After mixing the above-mentioned components according to the production method, granules are produced and can be used for the production of health food compositions according to the usual methods.

(Formulation example 7. Production of health drink)
5,8-hydroxy-1,4-naphthoquinone 100 mg
Vitamin C 15g
Vitamin E (powder) 100g
Iron lactate 19.75g
Zinc oxide 3.5g
Nicotinamide 3.5g
Vitamin A 0.2g
Vitamin B ₁ 0.25g
Vitamin B ₂ 0.3g
Water A suitable amount After mixing the above ingredients according to the normal health drink manufacturing method, stir and heat at 85 ° C. for about 1 hour, then filter the manufactured solution into a sterilized 2 liter container, After sealed sterilization, it is stored in a refrigerator, and then used for producing the health drink composition of the present invention.

  The above composition ratio is a mixed composition of components that are relatively suitable for taste drinks as a preferred embodiment, but depending on the regional and ethnic preference, such as demand hierarchy, demand country, usage, etc. There is no problem even if the mixing ratio is arbitrarily changed.

  As mentioned above, the naphthoquinone compound of the present invention suppresses the aggregation of beta amyloid known as the cause of Alzheimer's disease, and confirms the cognitive function recovery effect such as inhibiting cytotoxicity caused by beta amyloid. Therefore, it can be usefully used as a pharmaceutical composition for preventing and treating cognitive impairment and a health functional food.

It is a figure which shows the inhibitory activity of beta amyloid aggregation by juglone. It is a figure which shows the inhibitory activity of the beta amyloid aggregation by 5, 8-hydroxy-1, 4- naphthoquinone. It is a figure which shows the inhibitory activity of the beta amyloid aggregation by 1, 2- naphthoquinone. It is a figure which shows the inhibitory effect of the naphthoquinone type compound with respect to the toxicity of beta amyloid. It is a figure which shows the cytotoxicity of a naphthoquinone type compound.

Claims (4)

  A naphthoquinone compound selected from juglone, 5,8-hydroxy-1,4-naphthoquinone (5,8-hydroxy-1,4-naphthoquinone), and 1,2-naphthoquinone (1,2-naphthoquinone) A pharmaceutical composition for preventing or treating a cognitive dysfunction-related disease comprising as an active ingredient.   The cognitive impairment related disease is Alzheimer-type dementia, cerebrovascular dementia, pick disease, Creutzfeldt-jakob disease, dementia due to head injury, or Parkinson's disease. The pharmaceutical composition according to claim 1.   Jugrone, 8-hydroxy-1,4-naphthoquinone (5,8-hydroxy-1,4-naphthoquinone), and 1,2-naphthoquinone (1,1) showing the effect of prevention and treatment of cognitive impairment related diseases A health functional food comprising, as an active ingredient, a naphthoquinone compound selected from 2-naphthoquinone).   The health functional food according to claim 3, which is a powder, granule, tablet, capsule, or beverage.

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