KR102021453B1 - Pharmaceutical Composition for Prevention or Treatment of Alzheimer's Disease Including Dendrobium nobile Extract - Google Patents

Abstract

The present invention relates to a pharmaceutical composition and health functional food for preventing or treating Alzheimer′s dementia containing a Dendrobium moniliforme extract as an active component. The pharmaceutical composition for preventing or treating Alzheimer′s dementia contains a single active component extracted from natural products, so that drug toxicity is significantly reduced. In addition, health functional food for preventing or treating Alzheimer′s dementia of the present invention contains components extracted from natural products, thereby exhibiting a significant effect that can be applied to health functional food.

Description

Pharmaceutical Composition for Prevention or Treatment of Alzheimer's Disease Including Dendrobium nobile Extract}

The present invention relates to a pharmaceutical composition and a dietary supplement for preventing or treating Alzheimer's dementia comprising an extract of Seokok as an active ingredient.

Dementia is a pathological phenomenon that can be distinguished from normal aging and, depending on its cause, it is classified as Alzheimer's disease, vascular dementia, other alcoholism, trauma, or aftereffects of Parkinson's disease. do. Alzheimer's dementia accounts for the largest proportion.

Tau protein is a type of microtubule binding protein that regulates exon transport and stabilizes microtubules. However, in Alzheimer's disease, tau protein is abnormally increased in phosphorylation and hyperphosphorylated tau protein aggregates in the form of paired helical filaments (PHFs). As a result, it is known that tau protein loses its function as a microtubule-binding protein, causing Alzheimer's disease.

To date, drug treatment for the treatment of dementia has been used to increase the concentration of acetylcholine in the brain by administering an acetylcholine precursor or a drug that inhibits the degradation of acetylcholine. Representative drugs include tacrine, donepezil, rivastigmine, galantamine, and the like.

Conventional dementia treatments are mainly cholinergic drugs, so they cannot be co-administered with other cholinergic drugs, and the effect of neutralizing the effects of anticholinergic drugs is a problem. Can be. In addition, the patient with a history of severe asthma or obstructive pulmonary disease has a disadvantage that must be used with caution.

Therefore, finding a drug with low toxicity while being able to effectively treat and prevent Alzheimer's dementia as a method different from existing therapeutic agents is the most important situation for overcoming the disease. In this respect, the method of extracting the active ingredient from the natural extract provides an advantage.

The inventors of the present invention, while studying the treatment and prevention of Alzheimer's disease of Dendrobium nobile , found an effective ingredient for the treatment of Alzheimer's dementia among the components present in the herbal medicine to complete the present invention.

Republic of Korea Patent Publication 2007-0031546

An object of the present invention is to provide a pharmaceutical composition for preventing or treating Alzheimer's dementia.

In addition, an object of the present invention is to provide a method for preparing a pharmaceutical composition for preventing or treating Alzheimer's dementia, including extracting, separating, and formulating an active ingredient in grains.

An object of the present invention is to provide a dietary supplement for preventing or improving Alzheimer's disease.

In order to achieve the problem to be solved of the present invention, the present invention provides a pharmaceutical composition for preventing or treating Alzheimer's dementia comprising the formula (1) and / or formula (2).

The present invention also provides a method for preparing a pharmaceutical composition for preventing or treating Alzheimer's dementia, including extracting, isolating and formulating an active ingredient in grains.

The present invention also provides a dietary supplement for preventing or improving Alzheimer's disease.

Since the pharmaceutical composition for preventing or treating Alzheimer's dementia of the present invention contains a single active ingredient extracted from natural products, drug toxicity is significantly reduced.

In addition, the health functional food for preventing or improving Alzheimer's dementia of the present invention includes a component extracted from natural products, thereby exhibiting a remarkable effect that can be applied to a health functional food.

1 is a view showing a manufacturing process of the grain extract according to Example 1.
Figure 2 is a diagram showing the component separation process of the Seokgok extract.
3 is a diagram showing a 1 H-NMR spectrum of the compound of the formula (1).
4 is a diagram showing a 13C-NMR spectrum result of the compound of Formula 1. FIG.
5 is a diagram showing a 1 H-NMR spectrum of the compound of the formula (2).
6 is a diagram showing a 13C-NMR spectrum result of the compound of Formula 2. FIG.
7 is a diagram showing the cell activity during the treatment of the Seokok methanol extract
Figure 8 is a diagram showing the cell activity in the treatment of each fraction of the Seokgok extract.
9 is a diagram showing the cell activity of the cell line treated with the compound of formula (1).
10 is a diagram showing the cell activity of the cell line treated with the compound of formula (2).
11 is a diagram showing the extent of tau protein hyperphosphorylation inhibited in the treatment of Seokok methanol extract by Western blot.
FIG. 12 is a diagram quantifying the AT8 western blot band of FIG. 11.
13 is a diagram showing the extent of tau protein hyperphosphorylation inhibited in the treatment of each fraction of the Seokok extract in Western blot.
FIG. 14 is a diagram quantifying the AT8 western blot band of FIG. 13. FIG.
FIG. 15 is a western blot showing the degree of tau protein hyperphosphorylation inhibited when treating a compound of Formula 1. FIG.
FIG. 16 is a diagram quantifying the AT8 western blot band of FIG. 15. FIG.
FIG. 17 is a western blot showing the degree of tau protein hyperphosphorylation inhibited when treating the compound of Formula 2. FIG.
FIG. 18 is a diagram quantifying the AT8 western blot band of FIG. 17.
19 is a diagram showing the extent of tau protein hyperphosphorylation when treated with dendrrobin in Western blot.
FIG. 20 is a diagram quantifying the AT8 western blot band of FIG. 19.

Hereinafter, the present invention will be described in more detail.

The present invention relates to a pharmaceutical composition for preventing or treating Alzheimer's dementia comprising a compound of Formula 1 and / or a compound of Formula 2.

In the present specification, unless otherwise specified, the compound of Formula 1 or Formula 2 is used to mean a pharmaceutically acceptable salt of each compound.

The salt of the compound of formula 1 or formula 2 included in the pharmaceutical composition or the nutraceutical of the present invention may be a physiologically acceptable salt with an inorganic acid, an organic acid, an inorganic base or an organic base.

Examples of the inorganic acid may include hydrochloric acid, bromic acid, sulfuric acid, and phosphoric acid, and the organic acid may be citric acid, acetic acid, lactic acid, tartariac acid, maleic acid, fumaric acid, formic acid, propionic acid. ), Oxalic acid, trifluoroacetic acid, benzoic acid, gluconic acid, methanesulfonic acid, glycolic acid, succinic acid, 4-toluenesulfonic acid, galluxuronic acid, embonic acid, glutamic acid or aspartic acid, and the like.

The compound of Formula 1 or Formula 2 may each or together act as an active ingredient of the pharmaceutical composition.

The significant effects of the compounds of formula 1 or formula 2 can be clearly contrasted when compared to Dendrobine. Dendrobine is an index component of Seokgok Extract and has a sesquiterpene alkaloid structure.

According to one experimental example of the present invention, unlike the compound of Formula 1 or Formula 2, Dendrobine did not inhibit hyperphosphorylation of tau protein at all (see FIGS. 19 and 20, Comparative Example 2).

Compound of Formula 1 or Formula 2 included in the pharmaceutical composition of the present invention is characterized in that isolated from Dendrobium nobile . Seokgok is a plant belonging to the orchid family and is cultivated in China, Japan, Taiwan, and Korea. Its roots have several thick roots and several stems grow up to 20cm high. Seokgok has been used for a long time as an antipyretic or antipyretic agent, but no single substance effective for preventing or treating Alzheimer's dementia has been reported.

In order to prepare an extract containing the compound of Formula 1 or Formula 2 included in the pharmaceutical composition of the present invention, cold extraction, warm extraction, thermal extraction, ultrasonic extraction, etc. may be utilized from the grains of the herbal state. For this purpose, a herbal extractor, an ultrasonic mill extractor or a fractionator may be used.

Separation of the compound of Formula 1 or Formula 2 as an active ingredient of the pharmaceutical composition of the present invention may be achieved by extraction with one or more solvents selected from C1 to C5 straight or branched alcohols. Preferably methanol is preferred. The methanol may be in a concentration of 10 to 99% (v / v), preferably 50 to 99% (v / v), more preferably 70 to 99% (v / v).

After extracting Seokgok with one or more solvents selected from C1 to C5 linear or branched alcohols, the extract was extracted, and then the Seokok residue was removed, filtered through a filter paper, and the filtrate was concentrated using a vacuum rotary concentrator or a vacuum dryer. , Can be stored at room temperature.

The extract is water, at least one solvent selected from the group consisting of C1 to C5 straight or branched alcohol, acetone and ethyl acetate or at least one solvent selected from the group consisting of hexane, dichloromethane, ethyl acetate, butanol and water The fractionation process can be carried out simultaneously or sequentially.

Preferably, the methanol extract of Seokgok is fractionated simultaneously or sequentially with one or more solvents selected from the group consisting of hexane, dichloromethane, ethyl acetate and water to separate the compound of Formula 1 or the compound of Formula 2.

The fraction may be concentrated using a vacuum rotary concentrator or a vacuum dryer, and then stored at room temperature.

Pharmaceutical compositions according to the invention may be formulated to include an inert carrier, diluent, or both.

Examples of the inert carrier or diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, corn starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl Cellulose, microcrystalline cellulose, polyvinylpyrrolidone, citric acid, tartaric acid, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, dextrin, calcium carbonate, propylene glycol, liquid paraffin, physiological saline Etc., but is not limited thereto.

In addition, the pharmaceutical compositions of the present invention include conventional fillers, extenders, binders, disintegrants, anticoagulants, lubricants, wetting agents, pH adjusting agents, nutrients, vitamins, electrolytes, alginic acid and salts thereof, pectic acid and salts thereof, protective colo Ride, glycerin, fragrances, emulsifiers or preservatives may further be included. Other suitable lubricants and additional excipients that can be used are described in the following documents. Handbook of Pharmaceutical Excipients, 7th Edition, American Pharmaceutical Association; The Theory and Practice of Industrial Pharmacy, 3th Edition, Lachman, Leon, 1976; Pharmaceutical Dosage Forms: Tablets Volume 1-3 Edition, Lieberman, Hebert A., et al., 1989; Modern Pharmaceutics, Banker, Gilbert and Rhodes, Christopher T, 1979; And Remington's Pharmaceutical Sciences, 15th Edition, 1975].

The pharmaceutical compositions according to the invention may be formulated into oral or parenteral preparations, including additives including carriers, diluents as exemplified above.

Formulations for oral administration include tablets, capsules, pills, powders, granules, suspending agents and syrups. Forms for parenteral administration may be in the form of creams, lotions, ointments, solutions, gels, cataplasmas, patches, aerosols, liquid extracts, elixirs, acupuncture, sachets, injections and the like.

In this case, the content of the compound of Formula 1 or Formula 2 in the pharmaceutical composition for preventing or treating Alzheimer's dementia is 0.001% to 99.9% by weight, 0.1% to 99% by weight, or 1% to 50% by weight. However, the present invention is not limited thereto, and the content of the compound may be appropriately adjusted to a desired content according to the use mode and method of use of the composition.

In addition, the pharmaceutical composition for preventing or treating Alzheimer's dementia of the present invention may further include a substance known in the art to have a known dementia therapeutic effect in addition to the active ingredient. Examples thereof include, but are not limited to, tacrine, donepezil, rivastigmine, galantamine, and the like.

Alzheimer's disease used in the present invention is dementia caused by Alzheimer's disease and is included in the scope of the present invention as long as it is dementia caused by hyperphosphorylation of tau protein.

A pharmaceutical composition for preventing or treating Alzheimer's dementia comprising the compound of Formula 1 and / or Formula 2 according to the present invention may be applied to an animal including a human.

The dosage of the pharmaceutical composition according to the present invention can be determined in consideration of the method of administration, the age, sex of the recipient, the severity, the condition of the patient, the absorption of the active ingredient in the body, the inactivation rate and the drug used in combination, and is effective for one day. 0.1 mg / kg (body weight) to 500 mg / kg (body weight), preferably 0.1 mg / kg (body weight) to 400 mg / kg (body weight) or more preferably 1 mg / kg (based on the component) Body weight) to 300 mg / kg (body weight), and the administration may be administered once or divided into several doses, but is not limited thereto.

According to the above method of taking or adjusting the dosage, the compound of Formula 1 or Formula 2 of the present invention may be included in the health functional food, thereby providing a health functional food. The health functional food may exhibit an Alzheimer's dementia prevention or improvement effect.

The compound of Formula 1 or Formula 2 of the present invention has a significantly lower toxicity compared to the organic synthetic compound synthesized by the chemical synthesis method, as extracted from the natural grains. According to one embodiment of the present invention, as well as the Seokkok solvent extract, a single effective ingredient of the compound of Formula 1 or Formula 2 showed little cytotoxicity at an effective concentration (see FIGS. 7 to 10). Therefore, the applicability as a dietary supplement is natural in view of the general public.

The pharmaceutical composition according to the present invention

i) extracting the grains with a straight or branched alcohol of 50% (v / v) to 99% (v / v) C1 to C5,

ii) simultaneously or sequentially fractionating the extract obtained in the above step with at least one solvent selected from the group consisting of hexane, dichloromethane, ethyl acetate, and water;

It may be prepared by a manufacturing method comprising a.

Hereinafter, the present invention will be described in detail with reference to Examples. However, the following examples are merely to illustrate the invention, the scope of the present invention is not limited by the following examples.

Example  One. Seokgok  Preparation of Extracts and Fractional Extracts

One. Dendrite  Preparation of Methanol Extracts

6 kg of dried grains were extracted with 95% methanol at room temperature for 1 day, filtered through a filter paper (Nalgene, New York, NY, USA), and the filtrate was concentrated using a vacuum rotary concentrator (EYELA, Tokyo, Japan). This process was repeated three times and the concentrate was stored at 4 ° C. until use. A total of 622.4 g of extract was obtained (see FIG. 1).

2. Dendrite  Preparation of Fraction Extract

The extract of Example 1-1 was partitioned into two solvents, each of which was not mixed by using a polarity difference. Specifically, the granules methanol extract obtained in Example 1.1 was concentrated by fractionation with n-hexane, dichloromethane, ethyl acetate, and water layers, and this process was repeated three times. The concentrate was stored at 4 ° C. until use (see FIG. 1).

Example  2. Component Separation of Extracts

The dichloromethane fractionation layer was divided into five fractions (DNC1 to DNC5) by silica gel column chromatography (dichloromethane: methanol = 100: 1 to 30: 1). Fraction FRH2 (1.6 g) was subjected to silica gel column chromatography (chloroform: methanol = 200: 1 to 50: 1) and divided into four fractions (DNC2-1 to DNC2-4). Silica gel column chromatography (hexane: ethyl acetate = 3: 1 to 1: 1) was performed on DNC2-4 to divide into 7 fractions (DNC2-4-1 to DNC2-4-7), and DNC2-4-4. Compound 1 (118 mg) was obtained. DNC2-1 (157 mg) was subjected to silica gel column chromatography (chloroform: methanol = 100: 1 to 10: 1) and divided into four fractions (DNC2-1-1 to DNC2-1-4). Four fractions (DNC2-1-1-1 to DNC2-1-1-4) were performed by silica gel column chromatography (hexane: acetone = 5: 1 to 1: 1) on DNC2-1-1 (70 mg). And DNC2-1-1-1 compound 2 (20 mg) was obtained (see FIG. 2).

Example  3. Structural Identification of Compounds of Formula 1

Compound 1 was isolated as a red powder. First, three aromatic protons (δH 9.36, δδH 7.34, and δδH 7.25) were identified by 1H-NMR. Other aromatic protons were observed at δδH 8.08 and δδH 7.96, and methoxyl groups were identified at δH 3.90. In 13C-NMR, 15 protons were identified, 8 quaternary carbons (δδc 180.7, δδc 159.1, δδc 189.9, δδc 127.3, δδc 123.3, δδc 159.8, δδc 139.4, δδc 129.7, 6 methcarbons (δδc 111.1, δδc 122.3, δδc 123.0, δδc 109.7, δδc 132.7, δδc 130.1), and one methoxyl group (δδc 56.4) (see Tables 1, 3 and 4).

Carbon number Compound 1 ¹ H ¹³ C One 180.7 2 159.1 3 6.30 (s) 111.1 4 189.9 4a 127.3 4b 123.3 5 9.36 (1H, d, J = 9.1 Hz) 122.3 6 7.34 (1H, doublet of doublets, J = 1.8 and 9.1 Hz) 123.0 7 10.45 (s) 159.8 8 7.25 (1H, doublet, J = 2.1 Hz) 109.7 8a 139.44 9 8.08 (1H, doublet, J = 8.4 Hz) 132.77 10 7.96 (1H, doublet, J = 8.4 Hz) 130.15 10a 129.7 OMe 3.90 (s) 56.4

By combining the results, the structure of the compound having the formula 1 was identified.

<Formula 1>

Example  4. Structural Identification of Compounds of Formula 2

Compound 2 was isolated as a red powder. First, two sets of aromatic protons (δH 9.12, δδH 7.22 / δδH 7.22, and δδH 8.25) were identified in 1H-NMR. Methoxyl groups were identified at δH 3.83 and δδH 3.82. In 13C-NMR, 15 protons were identified, 9 quaternary carbons (δδc 189.9, δδc 159.9, δδc 1192.8, δδc 130.1, δδc 127.5, δδc 182.3, δδc 101.3, δδc 150.2, δδc 134.5), and 5 methcarbons ( δc 103.6, δδc 107.6, δδc 126.4, δδc 149.5, δδc 141.4), and two methoxyl groups (δc 4.55, δδc 56.4). (Table 1, FIG. 3 and FIG. 4).

Carbon number Compound 1 ¹ H ¹³ C One 189.9 2 159.9 3 6.09 (S) 103.6 4 192.8 4a 130.1 4b 127.5 5 9.12 (1H, doublet of doublets, J = 0.7 and 9.1 Hz) 107.6 6 7.22 (1H, doublet, J = 9.1 Hz) 126.4 7 9.649 (-OH) 182.3 8 101.3 8a 150.2 9 8.25 (1H, doublet of doublets, J = 0.7 and 9.0 Hz) 149.5 10 7.99 (1H, doublet, J = 9.1 Hz) 141.4 10a 134.5 OMe 3.83 (s) 56.4   OMe ｀ 3.80 (s) 61.3

By combining the results, the structure of the compound having the formula 2 was identified.

<Formula 2>

Experimental Example  One. extract, Fraction  And separation, Identified  Determination of the Toxicity of the Compound

-CHO 세포를 24시간 배양한 후, 5 mg/ml 농도의 MTT 용액을 넣고 4시간 배양하였다. 배지를 제거하고 DMSO를 넣어 30분간 용해시킨 후 Emax precision microplate reader (Molecular Devices, CA, USA)를 이용하여 540 nm에서 흡광도를 측정하였다. 석곡의 메탄올 추출물 및 분획물 뿐 아니라, 화학식 1 및 화학식 2의 화합물에서도 의미 있는 세포독성이 관찰되지 않았다(도 7 내지 10 참조). MTT-based cytotoxicity assay was performed to examine the cytotoxicity of extracts, fractions, isolates and identified compounds. APP treated with compound of formula 1

After culturing CHO cells for 24 hours, 5 mg / ml MTT solution was added and incubated for 4 hours. The medium was removed, dissolved in DMSO for 30 minutes, and the absorbance was measured at 540 nm using an Emax precision microplate reader (Molecular Devices, CA, USA). Significant cytotoxicity was not observed in the methanol extracts and fractions of the grains, as well as the compounds of Formula 1 and Formula 2 (see FIGS.

Experimental Example  2. extract, Fraction  And separation, Identified  Compound Tau protein Hyperphosphorylation Inhibitory ability  observe

Western blot experiments using HT22 cells were used to determine the inhibitory effect of tau protein hyperphosphorylation of compounds 1 to 2. In other words, induction of hyperphosphorylation of tau protein was induced by 18 hours treatment of okadaic acid (60 nM) on HT22 cells, and an antibody called AT8 was used to confirm hyperphosphorylation. It is an antibody that recognizes phosphorylation of Thr205 residue. That is, compounds 1 and 2 (0.5, 1, 2 ug / mL) is pretreated with HT22 cells for one hour, followed by okadaic acid for 18 hours. Then, the cells were dissolved in Laemmli sample buffer to make samples for Western blot, applied to SDS-PAGE, separated by protein size, and transferred to PVDF membrane. Confirmed as.

As a result, the band recognized as antibody AT8 was significantly increased when treated with okadaic acid compared with the DMSO-only group. In contrast, the experimental groups pretreated with Compounds 1 and 2 were found to be proportional to the amount of protein superphosphorylated in a concentration-dependent manner. At the concentrations of 1 and 2 ug / mL in both Compounds 1 and 2, the amount of superphosphorylated tau protein was significantly decreased, especially in the 2 ug / mL treatment group, 70% less than the okadaic acid treatment group. It showed a remarkable effect of decreasing than the control group. As a result, both compounds 1 and 2 showed the results that effectively inhibit the hyperphosphorylation of tau protein (Figs. 11 to 18).

Comparative Experiment  One. Of Dendrobine Tau protein Hyperphosphorylation Inhibitory ability  observe

We observed the ability of Dendrobine to inhibit the hyperphosphorylation of tau protein, which is widely known to be found in grains. According to the same experimental method as in Experiment 1, Dendrobine was treated to cells to 0.5 to 4 ug / mL, the cells were cultured, and the amount of tau protein was measured by Western blotting. As a result, Dendrobine showed no inhibitory effect on tau protein phosphorylation.

Production Example  One. Powder  Produce

Compound of Formula 1 or 2 1 mg Lactose 300mg Talc 10 mg

The above ingredients were mixed and filled in an airtight cloth to prepare a powder.

Production Example  2. Manufacture of tablets

Compound of Formula 1 or 2 1 mg Lactose 100mg Corn starch 100 mg Magnesium Stearate 2 mg

After mixing the above components was prepared by tableting according to the conventional tablet manufacturing method.

Production Example  3. Preparation of Capsule

Compound of Formula 1 or 2 1 mg Crystalline cellulose 3 mg Lactose 14.8 mg Magnesium Stearate 0.2 mg

The above ingredients were mixed and then filled into gelatin capsules.

Production Example  4. Preparation of Injectables

(After injection filtration)
Compound of Formula 1 or 2 0.5 mg Mannitol 200 mg Na ₂ HPO ₄ 12H ₂ O 30 mg

According to the conventional method for preparing an injection, the amount of the above ingredient was prepared per ampoule (2 ml).

Production Example  5. Preparation of dietary supplement containing the compound of formula 1 or 2

Compound of Formula 1 or 2 0.1 mg Vitamin c 50 mg Folic acid 50 μg Calcium Pantothenate 0.5 mg Biotin 10 μg Lactose 100 mg Magnesium Stearate 2 mg

According to the conventional manufacturing method of health functional food, the health functional food was prepared by tableting with the said component content.

Claims (14)

A pharmaceutical composition for preventing or treating Alzheimer's dementia comprising a compound of Formula 1 or a pharmaceutically acceptable salt thereof.

Formula 1

A pharmaceutical composition for preventing or treating Alzheimer's dementia comprising a compound of Formula 2 or a pharmaceutically acceptable salt thereof.

Formula 2

The method according to claim 1 or 2,
Compound of Formula 1 or Formula 2 is characterized in that isolated from the dendrobium (Dendrobium nobile), Alzheimer's dementia preventive or therapeutic pharmaceutical composition.
The method of claim 3,
Separation of the compound of Formula 1 or Formula 2 is characterized in that the extraction using water, C1 to C5 linear or branched alcohol, acetone and ethylacetate using at least one solvent selected from the group consisting of, Alzheimer's dementia prevention Or therapeutic pharmaceutical compositions.
The method of claim 4, wherein
C1 to C5 linear or branched alcohol is a pharmaceutical composition for preventing or treating Alzheimer's dementia, characterized in that methanol.
The method of claim 3,
Separation of the compound of Formula 1 or Formula 2 is characterized in that the extraction using at least one solvent selected from the group consisting of hexane, dichloromethane, ethyl acetate, butanol and water, Alzheimer's dementia preventive or therapeutic pharmaceutical composition .
The method of claim 3,
Separation of the compound of Formula 1 or Formula 2 is achieved by simultaneously or sequentially fractionating the methanol extract of Seokok with at least one solvent selected from the group consisting of hexane, dichloromethane, ethyl acetate and water, Alzheimer's Pharmaceutical composition for preventing or treating dementia.
The method according to claim 1 or 2,
The pharmaceutical composition is an inert carrier, diluent, or both, Alzheimer's dementia preventive or therapeutic pharmaceutical composition.
The method according to claim 1 or 2,
The pharmaceutical composition is characterized in that the formulation oral or parenteral formulation, Alzheimer's dementia preventive or therapeutic pharmaceutical composition.
The method according to claim 1 or 2,
The pharmaceutical compositions are tablets, capsules, pills, powders, granules, suspending agents and syrups, in the form of creams, lotions, ointments, solutions, gels, cataplasmas, patches, aerosols, fluid extracts, elixirs, A pharmaceutical composition for preventing or treating Alzheimer's dementia, characterized in that it is formulated in an agent selected from the group consisting of acupuncture, sachets and injections.
The method according to claim 1 or 2,
The pharmaceutical composition is characterized in that it further comprises at least one active ingredient selected from the group consisting of tacrine, donepezil, rivastigmine and galantamine, pharmaceutical composition for preventing or treating Alzheimer's dementia.
i) extracting the grains with a straight or branched alcohol of 50% (v / v) to 99% (v / v) C1 to C5,
ii) simultaneously or sequentially fractionating the extract obtained in the above step with at least one solvent selected from the group consisting of hexane, dichloromethane, ethyl acetate, and water;
A method for preparing a pharmaceutical composition for preventing or treating Alzheimer's dementia according to claim 1 or 2.
A dietary supplement for preventing or improving Alzheimer's dementia comprising a compound of Formula 1 or Formula 2.

Formula 1

Formula 2

The method of claim 13,
The compound of formula 1 or formula 2 is Alzheimer's dementia prevention or improvement health functional food, characterized in that extracted from grains.

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