KR20090078939A - Composition comprising a polyphenol compound for preventing or treating a neurodegenerative disease - Google Patents

Abstract

A composition for preventing and treating neutodegenerative disease, which contains a polyphenol compound as an active ingredient is provided to have the effects of beta-amyloid coagulation inhibition, caspase-3 activity suppression and acetylcholinesterase activation suppression. A composition for preventing and treating neurodegenerative diseases comprises salvianolic acid, bakuchiol, epsilon-viniferin, rhapontigenin, piceatannol, luteolin, myricetin, or their mixture as an active ingredient. The neurodegenerative diseases are Alzheimer's disease, Pick's disease, Creutzfeldt-jakob, Parkinson's disease, Lou Gehrig's Disease, or Huntington's disease. The composition suppresses BACE-1[beta-site APP(amyloid precursor protein)-cleaving enzyme 1], caspase or acetylcholine esterase. The composition further comprises medicinal herb. The medicinal herb is Salviae Miltiorrhizae Radix, Psoraleae Semen, Vitidis Fructus, Rhei Rhizoma, Digitalis Folium, Schizonepeta Herba, Taraxaci Herba, Humuli Herba, Lonicerae Folium or their mixture.

Description

COMPOSITION COMPRISING A POLYPHENOL COMPOUND FOR PREVENTING OR TREATING A NEURODEGENERATIVE DISEASE}

The present invention relates to a composition for the prevention or treatment of degenerative brain diseases, comprising a polyphenolic compound as an active ingredient.

Dementia is a gradual deterioration of memory and cognitive abilities that impairs daily life. Dementia can be classified into vascular dementia and Alzheimer's dementia. In vascular dementia, cerebral infarction or stroke occurs mainly due to blood clots formed in blood vessels, and it is known that brain cells around the affected area are damaged to cause symptoms such as memory loss. On the other hand, Alzheimer's dementia, which accounts for much more than vascular dementia, progresses slowly with symptoms such as memory loss, personality changes, and poor thinking, but most patients die of pneumonia within 8 to 10 years. It is known. The disease is estimated to have 3.5 to 10% of senior citizens over 65 years of age worldwide, and there are an estimated 4 million patients in the United States alone. to be. Recent epidemiologic studies have reported that risk factors for cerebrovascular diseases, such as hypertension, diabetes, hyperlipidemia, and heart disease, increase the incidence of Alzheimer's as well as vascular dementia. .

As a characteristic lesion of Alzheimer's dementia, amyloid plaques including β-amyloid, neurofibrillary tangles, etc. are formed in the brain tissue to cause inflammatory reactions in immune cells, and Ca ^{2 In} addition to destroying the ⁺ channel, it has been reported to reduce the amount of the neurotransmitter, acetylcholine, causing memory and cognitive decline. Thus, drugs capable of blocking beta-amyloid production in the brain or eliminating insoluble beta-amyloid aggregates are useful as therapeutic agents for Alzheimer's dementia (Hardy J. & Selkoe DJ, Science 297: 353-6, Singer O. et al., Nat Neurosci 8: 1343-9, 2005; Maiorrini AF et al., J Clin Pharm Ther 27: 169-83, 2002; Aisen PS, CNS Drugs 19: 989-96, 2005 and Pollack SJ & Lewis H., Curr Opin Investig Drugs 6: 35-47, 2005). Recently, attempts to develop beta-secretase (B-secretase / BACE1) or gamma-secretase (γ-secretase) inhibitors that promote beta-amyloid production have been rapidly increasing. It is expected to be developed successfully.

The modern medical view of cognitive deterioration caused by Alzheimer's dementia (AD) considers the widespread degeneration and loss of brain cholinergic neurons as the main cause of cognitive decline and is not compromised as a way to overcome it. The main focus is to develop drugs that can partially restore damaged cognitive function by increasing the activity of cholinergic nervous system. Four drugs currently recognized by the US Food and Drug Administration (FDA) for the treatment of Alzheimer's dementia: tacrine, rivastigmin, donepezil, and galanthamine are all acetylcholine Acetylcholinesterase inhibitors that enhance cognitive function by inhibiting the activity of degrading enzymes (Scarpini E. et al., Lancet Neurol 2: 539-47, 2003); Hashimoto M. et al. , Am J Psychiatry 162: 676-82, 2005 and Bartus RT, Exp Neurol 163: 495-529, 2000). In addition, researches on inhibitors of acetylcholinesterase inhibitors as well as development of agonists or antagonists for various receptors that act on the cholinergic nervous system, particularly muscarinic receptors, have been actively conducted (Anagnostaras SG et al, Nat Neurosci 6: 51-58, 2003; see Shino T. et al., J Neurosci 30: 11194-11200, 2005 and Wess J., Annu Rev Pharmacol Toxicol 44: 423-450, 2004).

Meanwhile, caspase, a protease, plays an important role in morphogenetic apoptosis in the brain nervous system. In particular, if a problem occurs during the apoptosis process associated with caspase-3, it may cause degenerative brain disease, which is reported to be caused by a continuous process of apoptosis. Representative degenerative brain diseases associated with caspase-3 include Alzheimer's disease (Kim TW et al., Science 277 (5324): 373-6, 1997); Gervais FG et al., Cell, 97 (3): 395-406, 1999; Walter J. et al., Proc Natl Acad Sci USA 96 (4): 1391-6, 1999 and Barnes NY et al., J Neurosci 18 (15): 5869-80, Parkinson's Disease (Takai N. et al., J Neurosci Res 54 (2): 214-22, 1998); Dodel RC et al., Mol Brain Res 64 (1): 141-8 , 1999), amyltrophic lateral sclerosis (see Pasinelli P. et al., Proc Natl Acad Sci US A. 95 (26): 15763-8, 1998), Huntington's disease (Goldberg YP). et al., Nature Genet. 13 (4): 442-9, 1996; Wellington CL et al., J Biol Chem. 273 (15): 9158-67, 1998 and Sanchez I. et al., Neuron. 22 (3): 623-33, 1999), and spinal cord injury (Crowe MJ et al., Nat Med. 3 (1): 73-6, 1997) and Human SL et al., J Neurosci Res. 50 (5): 798-808, 1997]). In order to develop a therapeutic agent for brain disease it is progressing steadily studies using cascaded phase -3 inhibitors.

Meanwhile, polyphenol-based compounds are naturally derived compounds contained in herbal medicines such as Salvia, Pagoji, Grape, Rhubarb, Foxglove, Foxglove, Pogongyoung, Yulcho, or Phosphorus.

Document 1 Hardy J. & Selkoe D.J., Science 297: 353-6, 2002

Singer O. et al., Nat Neurosci 8: 1343-9, 2005

Document 3 Maiorrini A.F. et al., J Clin Pharm Ther 27: 169-83, 2002

Aisen P.S., CNS Drugs 19: 989-96, 2005

[Reference 5] Pollack S.J. & Lewis H., Curr Opin Investig Drugs 6: 35-47, 2005

Scarpini E. et al., Lancet Neurol 2: 539-47, 2003

Hashimoto M. et al., Am J Psychiatry 162: 676-82, 2005

8 Bartus R.T., Exp Neurol 163: 495-529, 2000

Document 9 Anagnostaras S.G. et al., Nat Neurosci 6: 51-58, 2003

10. Shinoe T. et al., J Neurosci 30: 11194-11200, 2005.

11 Wess J., Annu Rev Pharmacol Toxicol 44: 423-450, 2004

12. Kim T. W. et al., Science 277 (5324): 373-6, 1997

Gervais F. G. et al., Cell, 97 (3): 395-406, 1999

Walter J. et al., Proc Natl Acad Sci U S A 96 (4): 1391-6, 1999

15 Barnes N. Y. et al., J Neurosci 18 (15): 5869-80, 1998

16. Takai N. et al., J Neurosci Res 54 (2): 214-22, 1998

Dodel R. C. et al., Mol Brain Res 64 (1): 141-8, 1999

Pasinelli P. et al., Proc Natl Acad Sci U S A. 95 (26): 15763-8, 1998

19 Goldberg Y. P. et al., Nature Genet. 13 (4): 442-9, 1996

20 Wellington C. L. et al., J Biol Chem. 273 (15): 9158-67, 1998

[0121] Sanchez I. et al., Neuron. 22 (3): 623-33, 1999

22. Crowe M. J. et al., Nat Med. 3 (1): 73-6, 1997

23 Shuman S. L. et al., J Neurosci Res. 50 (5): 798-808, 1997

It is an object of the present invention to provide a pharmaceutical composition capable of effectively preventing or treating degenerative brain diseases.

Another object of the present invention to provide a food composition that can effectively prevent or improve degenerative brain disease.

In accordance with the above object, the present invention provides a pharmaceutical composition for the prevention or treatment of degenerative brain diseases, including a polyphenolic compound.

In accordance with another object, the present invention provides a food composition for preventing or improving degenerative brain disease, including a polyphenolic compound.

Since the composition comprising the polyphenol-based compound according to the present invention exhibits the effects of inhibiting aggregation of beta amyloid (β-amyloid), inhibiting caspase-3 enzyme activity, and inhibiting acetylcholinesterase enzyme activity. It can be usefully used as a prophylactic or therapeutic agent for degenerative brain diseases.

The present invention provides a composition for the prevention or treatment of degenerative brain disease, comprising a polyphenolic compound as an active ingredient.

The polyphenol-based compound is salvianolic acid (salvianolic acid), bakuchiol (bakuchiol), epsilon-viniferin (ε-viniferin), rapontigenin (rhapontigenin), picetanol (piceatannol), luteolin (luteolin), It is characterized in that it is selected from the group consisting of myricetin (myricetin) and mixtures thereof.

The salvianolic acid, bakuchiol, epsilon-viniperin, lapontigenin, pisatanol, luteolin, myrithinin is the same as the formula 1-7:

The polyphenol-based compound exhibits the effect of inhibiting the enzymatic activity of BACE-1 (beta-site amyloid precursor protein) -cleaving enzyme 1), caspase and acetylcholine esterase, and thus the polyphenol-based compound and these The composition of the present invention containing a mixture of as an active ingredient is excellent prophylaxis against degenerative brain diseases such as Alzheimer's disease, pick disease, Creutzfeldt-jakob disease, Parkinson's disease, Lou Gehrig's disease or Huntington's disease It has a therapeutic effect.

The composition containing the compound of the present invention or a mixture thereof may be mixed with a suitable pharmaceutically acceptable carrier or excipient or diluted with a diluent according to a conventional method to prepare a pharmaceutical composition having the above function. Examples of suitable carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, malditol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, Methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. The pharmaceutical composition may further include fillers, anti-coagulants, lubricants, wetting agents, fragrances, emulsifiers, preservatives and the like.

The pharmaceutical compositions of the present invention may be formulated using methods well known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal. The formulations may be in the form of tablets, pills, powders, sachets, elixirs, suspensions, emulsions, solutions, syrups, aerosols, soft or hard gelatin capsules, sterile injectable solutions, sterile powders and the like.

The pharmaceutical composition of the present invention may comprise the polyphenolic compound in an amount of 0.01 to 10% by weight, preferably 0.01 to 1% by weight of the total weight.

The pharmaceutical compositions of the invention can be administered via several routes including oral, transdermal, subcutaneous, intravenous or intramuscular. A typical daily dosage of the pharmaceutical composition of the present invention is in the range of 0.01 to 10 mg / kg body weight, preferably 0.01 to 1.0 mg / kg body weight, based on the active ingredient, and may be administered once or in several doses. . However, the actual dosage of the active ingredient should be determined in light of several relevant factors such as the route of administration, the age, sex and weight of the patient, and the severity of the disease, and therefore the dosage limits the scope of the invention in any aspect. It is not.

Also in the present invention, the prevention of degenerative brain diseases, including polyphenolic compounds, ie salvianolic acid, bakuchiol, epsilon-viniferin, lapontigenin, picetanol, luteolin, myricetin or mixtures thereof Provided are food or beverage compositions for improvement.

Examples of the foods to which the polyphenolic compound of the present invention may be added to exhibit the above effects include, for example, various foods, beverages, snacks, sweets, gums, ice creams, tea bags, instant teas, granules, flavors, and vitamins. Compounds and other health supplements, but are not limited thereto.

The polyphenol-based compound of the present invention or a mixture thereof may be added to a raw material during food preparation or appropriately mixed with cooked food to prepare the above-mentioned food or beverage for health promotion. In this case, the amount of salvianolic acid, bakuchiol, epsilon-viniferin, lafontigenin, piaceanol, luteolin, myricetin or mixtures thereof in the finally prepared food or beverage is generally the total food weight for health foods. 0.01 to 10% by weight, preferably 0.01 to 1% by weight, and in the case of health drinks in the range of 0.01 to 1 g, preferably 0.01 to 0.1 g based on 100 ml.

The pharmaceutical composition, or food or beverage composition of the present invention may further include other medicinal herbs or powders or extracts thereof that are pharmaceutically acceptable to enhance or supplement the desired effect, and representative examples of such herbal medicines include Salviae Miltiorrhizae Radix , Pagoji ( Psoraleae Semen ), Grapes ( Vitidis Fructus ), Rhubarb ( Rhei Rhizoma ), Digitalis Folium , Schizonepeta Herba , Taraxaci Herba , Humuli Herba Lonicerae Folium ). The herbal medicines can be used independently or in combination in amounts of 0.1 to 30% by weight, preferably 1 to 10% by weight, based on the total weight of the composition.

Hereinafter, the present invention will be described in more detail based on the following examples. However, the following examples are not intended to limit the invention only.

Example

Example 1: Confirmation of BACE-1 Inhibitory Effect of Polyphenol-Based Compound

BACE-1 inhibitory effects of salvianolic acid, bakuchiol, epsilon-viniperin, lapontigenin, piaceanol, luteolin and myricetin, which are polyphenolic compounds, were measured as follows.

BACE-1 inhibitory effect was measured using the BACE-1 fret assay kit (BACE-1 FRET Assay Kit, PanVera (registered trademark)). Specifically, 10 ul of rhodamine-EVNDAEFK-quencher (final concentration 250 nM), a BACE-1 substrate solution, was used as a test compound at the desired concentrations of salvianolic acid, bakuchiol, epsilon-viniferin, lapontigenin, and picetanol. 10 μl of luteolin and myricetin were added, followed by 10 μl of human recombinant BACE-1 (final concentration 0.3 unit / mL) solution as BACE-1 enzyme, followed by incubation at room temperature for 60 minutes. Immediately after completion of the incubation, 10 μl of 2.5 M sodium acetate was added to the reaction solution as a reaction stop solution, and the fluorescence was measured at 545 nm (excitation wavelength) and 585 nm (emission wavelength) using a FlexStation. Enzyme activity was measured. The total volume of the reaction mixture was 40 μl, run on 384 black microwell plates, and 50 mM sodium acetate (pH 4.5) was used as the BACE-1 assay buffer. Detailed compositions of the BACE-1 enzyme, substrate solution, reaction stop solution, and assay buffer used in Example 1 are shown in Table 1 below.

Specifically, BACE-1 enzyme activity was confirmed by measuring the amount of substrate degradation at the end of the enzyme reaction by fluorescence analysis. The test was performed by comparing the enzyme activity of the control group without the test compound with the enzyme activity of the test group with the test compound. The enzyme inhibition rate of the compound was converted. First, the BACE-1 inhibition rate of the test compound was measured at the concentrations of 1 μg / ml and 100 μg / ml, and the test compound was diluted in steps of 7 to 8 for test compounds that exhibited 50% or more inhibitory effect at each concentration. The enzyme inhibition rate according to the gradient was measured, and the IC ₅₀ (50% enzyme inhibition concentration) value of each test compound was confirmed by linear regression analysis on the dose-response curve. As a result, it was confirmed that each compound inhibits the activity of BACE-1 in a concentration-dependent manner, the IC ₅₀ value of each compound is shown in Table 2 below.

As shown in Table 2, salvianolic acid, bakuchiol, epsilon-viniferin, lafontigenin, piaceanol, luteolin and myricetin all effectively inhibit BACE-1 activity, thus preventing and treating degenerative brain diseases. Can be effective.

Example 2: Confirmation of the inhibitory effect of acetylcholine esterase of the polyphenol-based compound

The inhibitory effects of acetylcholine esterases of salvianolic acid, bakuchiol, epsilon-viniferin, lapontigenin, piaceanol, luteolin and myricetin, which are polyphenolic compounds, were measured as follows.

First, 100 μl reaction solution containing Amplex Red reagent, Horseradish peroxidase (HRP), choline oxidase and acetylcholine 100 μl of 0.2 U / mL acetylcholinesterase solution (100 μl) and test compounds, ie salvianolic acid, bakuchiol, epsilon-viniperin, lapontigenin, picetanol, luteolin and myricetin, respectively. Add and incubate for 30 minutes at room temperature. After the incubation was completed, enzyme activity was measured by measuring fluorescence at 563 nm (excitation wavelength) and 587 nm (emission wavelength) using Victor ² (Victor ² , Wallac). The total volume of the reaction mixture was 300 μl and performed on a 96-well plate. The enzyme, substrate and assay buffer used in Example 2 were purchased from Molecular Probes (Molecular Probes, Eugene, OR, USA), and detailed compositions are shown in Table 3 below.

Specifically, the enzyme activity of acetylcholine esterase was confirmed by fluorescence analysis of the amount of substrate degradation at the end of the enzyme reaction. The enzyme activity of the control group without the test compound was compared with that of the test group with the test compound. The enzyme inhibition rate of the test compound was converted. First, the inhibition rate of acetylcholinesterase of the test compound was measured at the concentrations of 1 μg / ml and 100 μg / ml, and the test compounds were diluted gradually in steps of 7 to 8 for test compounds showing 50% or more inhibitory effect at each concentration. The enzyme inhibition rate according to the concentration gradient was measured, and the IC ₅₀ (50% enzyme inhibition concentration) value of each test compound was confirmed by linear regression analysis on the dose-response curve. As a result, it was confirmed that each compound inhibited the activity of acetylcholine esterase in a concentration-dependent manner, the IC ₅₀ value of each compound is shown in Table 4 below.

As shown in Table 4, salvianolic acid, bakuchiol, epsilon-viniferin, lafontigenin, piaceanol, luteolin and myricetin all effectively inhibit acetylcholinesterase activity, thereby preventing and preventing degenerative brain diseases. May have a therapeutic effect.

Example 3: Confirmation of the caspase-3 inhibitory effect of the polyphenolic compound

The caspase-3 inhibitory effect of salvianolic acid, a polyphenolic compound, was measured as follows.

First, caspase-3 enzyme quantification was performed on 96-well plates, specifically 20 mM HEPES / KOH (pH 7.5), 10% sucrose, 10 mM DTT, 0.2 mM EDTA, 0.1% CHAPS (3-[( In 200 µl of the reaction solution containing 3-cholamidopropyl) dimethylammonio] -1-propane sulfonate), 20 µl of salvianolic acid, 100 ng of human recombinant Caspase-3 (from Sigma) and 2.5 µM of Ac-DEVD- as substrate AFC (benzyloxycarbonyl-Asp-Glu-Val-Asp-7-amino-4-trifuoromethyl-coumarin, Sigma) was added. The substrate was used by diluting Ac-DEVD-AFC in DMSO at a concentration of 2.5 mM and storing it at -20 ° C with DMSO. After incubating the reaction solution at 37 ° C. for 1 hour, enzyme activity was measured by measuring fluorescence at 400 nm (excitation wavelength) and 510 nm (emission wavelength) using Victor ² (Wallac). IC ₅₀ values were calculated by nonlinear regression analysis using Prism (Prism, Graphpad software Inc., USA).

Specifically, the caspase-3 enzyme activity was confirmed by fluorescence analysis of the amount of substrate degradation at the end of the enzyme reaction, and the enzyme activity of the control group without salvianolic acid and the test group with salvianolic acid were added. In comparison, the enzyme inhibition rate of salvianolic acid was converted. First, the caspase-3 inhibition rate of salvianolic acid was measured at concentrations of 1 μg / ml and 100 μg / ml. For salvianolic acid showing an inhibitory effect of 50% or more at each concentration, the salvianolic acid was gradually diluted to 7 to 7 The enzyme inhibition rate was measured according to the concentration gradient of 8 steps, and the IC ₅₀ (50% enzyme inhibition concentration) value of salvianolic acid was confirmed by linear regression analysis of the dose-response curve. As a result, it was confirmed that salvianolic acid inhibited caspase-3 activity in a concentration-dependent manner, and IC ₅₀ values of salvianolic acid are shown in Table 5 below.

As shown in Table 5, salvianolic acid effectively inhibits caspase-3 enzyme activity and thus may exhibit a prophylactic and therapeutic effect of degenerative brain disease.

Formulation Examples

Pharmaceutical formulations and food formulations were prepared using polyphenolic compounds selected from salvianolic acid, bakuchiol, epsilon-viniperin, lafontigenin, piaceanol, luteolin, myrithinin and mixtures thereof.

Production Example 1 Powder

The powders were prepared by mixing the following ingredients and then filling the airtight cloth according to a conventional powder preparation method:

Polyphenol Compound Active Ingredient 2 g

1 g lactose

Preparation Example 2 Tablet

The tablets were prepared by mixing the following ingredients and then tableting according to the conventional tablet preparation method:

Polyphenol Compound Active Ingredient 100 mg

100 mg corn starch

Lactose 100 mg

2 mg magnesium stearate

Preparation Example 3 Capsule

The capsules were prepared by mixing the following ingredients and filling the gelatin capsules according to a conventional capsule preparation method:

Polyphenol Compound Active Ingredient 100 mg

100 mg corn starch

Lactose 100 mg

2 mg magnesium stearate

Production Example 4 Injection

Injectables were prepared by dissolving the active ingredient in distilled water for injection and adjusting the pH to about 7.5 according to a conventional injection method, and then filling the 2 ml volume of the ampoule with sterilized distilled water and sterilizing the following remaining ingredients:

Polyphenol Compound Active Ingredient 100 mg

Suitable amount of distilled water for injection

pH adjuster

<Manufacture example 5> Wire type

Brown rice, barley, glutinous rice, and yulmu were alphad by a known method, and then dried and roasted to make a powder having a particle size of 60 mesh. Black beans, black sesame seeds, and perilla were also steamed and dried in a known manner, and then ground to a powder having a particle size of 60 mesh.

The grains, seeds, and polyphenol compounds prepared above were blended in the following ratio to form granules.

Cereals: Brown rice 30% by weight, barley 15% by weight, barley 20% by weight, glutinous rice 9% by weight,

Seeds: perilla 7% by weight, black beans 8% by weight, black sesame 7% by weight,

3% by weight of polyphenol compound powder, 0.5% by weight of ganoderma lucidum, 0.5% by weight of sulfur

Preparation Example 6 Chewing Gum

Chewing gum was prepared in a conventional manner by combining 20% by weight of the gum base, 76.9% by weight of sugar, 1% by weight of perfume, and 2% by weight of water with 0.1% by weight of the polyphenolic compound of the present invention.

Production Example 7 Candy

Candy was prepared in a conventional manner by combining 60% by weight of sugar, 39.8% by weight of starch syrup, 0.1% by weight of perfume, and 0.1% by weight of polyphenol compound powder of the present invention.

Production Example 8 Biscuits

Force 25.59% by weight, 22.22% by weight of gravity, 4.80% by weight, white salt 0.73% by weight, 0.78% by weight, palm shortening 11.78% by weight, ammonium 1.54% by weight, 0.17% by weight sodium bisulfite 0.16% by weight , Rice flour 1.45%, Vitamin B₁0.0001%, Vitamin B₂0.0001%, Milk flavor 0.04%, Water 20.6998%, Whole milk powder 1.16%, Substitute milk powder 0.29%, Monobasic calcium phosphate 0.03% , Biscuits were prepared in a conventional manner by combining 0.29 wt% of spray salt, 7.27 wt% of spray oil, and 1 wt% of the polyphenol compound of the present invention.

<Manufacture example 9> Healthy drink

0.26% by weight of honey, 0.0002% by weight of thioctoamide, 0.0004% by weight of nicotinic acid, 0.0001% by weight of sodium riboflavinate, 0.0001% by weight of pyridoxine hydrochloride, 0.001% by weight of inositol, 0.002% by weight of orthoic acid and 98.7362% by weight of water 1 wt% of the polyphenol compound was formulated to prepare a health beverage in a conventional manner.

Preparation Example 10 Health Supplement

55% by weight of spirulina, 10% by weight of guar gum enzyme digestion, 0.01% by weight of vitamin B₁ hydrochloride, 0.01% by weight of vitamin B6 hydrochloride, 0.23% by weight of DL-methionine, 0.7% by weight of magnesium stearate, 22.2% by weight of lactose and 1.85% by weight of corn starch And blended 10% by weight of the polyphenolic compound of the present invention to prepare a tablet-type health supplement in a conventional manner.

Claims (7)

As active ingredients, salvianolic acid, bakuchiol, epsilon-viniferin, rhapontigenin, piceatannol, luteolin, and myricetin ( Myricetin) and a mixture of these, a polyphenol-based compound selected from the group consisting of, a pharmaceutical composition for the prevention or treatment of degenerative brain diseases. The method of claim 1, The degenerative brain disease is selected from the group consisting of Alzheimer's disease, pick disease, Creutzfeldt-jakob disease, Parkinson's disease, Lou Gehrig's disease and Huntington's disease. The method of claim 1, A composition characterized in that it exhibits a prophylactic or therapeutic effect of degenerative brain disease by inhibiting BACE-1 (beta-site amyloid precursor protein) -cleaving enzyme 1), caspase or acetylcholinesterase enzyme. Prevention of degenerative brain disease, comprising a polyphenolic compound selected from the group consisting of salvianolic acid, bakuchiol, epsilon-viniferin, lapontigenin, piaceanol, luteolin, myricetin and mixtures thereof as an active ingredient Or food composition for improvement. The method of claim 4, wherein The composition further comprises a herbal medicine. The method of claim 5, wherein The saengyakjae the Salvia (Salviae Miltiorrhizae Radix), pagoji (Psoraleae Semen), grapes (Vitidis Fructus), rhubarb (Rhei Rhizoma), foxglove leaf (Digitalis Folium), mold opening (Schizonepeta Herba), pogongyoung (Taraxaci Herba), yulcho (Humuli Herba ), Lonicerae Folium , and mixtures thereof. The method of claim 6, The herbal composition is characterized in that the form of a powder or extract.