KR20070017448A - Compound for improving Alzheimer Desease containing inhibitors of Cholinesterase activity extracted from marin plants and cognition ability - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for improving Alzheimer's dementia and cognitive ability, which has a cholinesterase (ChE) inhibitory activity, and a pharmaceutically acceptable salt or hydrate thereof, extracted from seaweed plants. It is about food. More specifically, improvement of Alzheimer's dementia containing Plastoquinone compound as an active ingredient, which is extracted from seaweed plants with selective butylcholinesterase (BuChE) inhibitory activity among the forms of cholinesterase (ChE) It relates to pharmaceutical compositions and dietary supplements. The composition for improving dementia of the present invention contains acetylcholine (ACh), a neurotransmitter in brain cells, containing an active ingredient that inhibits the activity of cholinesterase (ChE) isolated from marine edible plants, economically and efficiently. In addition, it can be used for the prevention and treatment of Alzheimer's dementia by selectively preventing the breakdown of butylcholine (BCh), and it is expected that the range of applications such as learning ability and memory improving agent will vary.

Alzheimer's, Cholinesterases, Plastoquinone Compounds, Acetylcholine (ACh), Butylcholine (BCh)

Description

Compound for improving Alzheimer Desease containing inhibitors of Cholinesterase activity extracted from marin plants and cognition ability}

1 is a graph showing the cognitive ability according to the repeated experiment of the formula (1) of the present invention.

2 is a graph showing the success rate according to the repeated experiment of the formula (1) of the present invention.

3 is a graph showing the average weight change by the repeated experiment of the formula (1) of the present invention.

The present invention relates to a pharmaceutical composition for improving Alzheimer's dementia and cognitive ability, which has a cholinesterase (ChE) inhibitory activity, and a pharmaceutically acceptable salt or hydrate thereof, extracted from seaweed plants. It is about food. More specifically, improvement of Alzheimer's dementia containing Plastoquinone compound as an active ingredient, which is extracted from seaweed plants with selective butylcholinesterase (BuChE) inhibitory activity among the forms of cholinesterase (ChE) It relates to pharmaceutical compositions and products.

As the quality of life improves with the development of the medical industry and rapid economic growth, various diseases and the elderly population are increasing. The average life span of humans has been extended, but the economic burden is increasing. One of them is senile dementia. More than 50% of them are Alzheimer's (AD) dementia. Pathologically, how dementia comes is not fully understood and there is no treatment. However, indirectly, the brains of dementia patients are known to have reduced 20% to 30% of choline acetyltransferase (ChAT), which synthesizes acetylcholine (ACh) than normal humans, and the neurotransmitter acetylcholine (ACh). The concentration was found to be reduced by 16-30%. Therefore, the method of injecting choline directly to increase the concentration of choline, which is a precursor to dementia patients, did not have much effect.

Therefore, as an indirect treatment method, studies using an inhibitor that inhibits choline esterase (ChE), an enzyme that hydrolyzes acetylcholine, a neurotransmitter, have been conducted. Cholinesterases have two forms, acetylcholinesterase (AChE) and butylcholinesterase (BuChE).

Previously, synthesis and development of acetylcholinesterase inhibitors have been the main focus, but recent studies are known to increase butylcholinesterase in the AD brain, which has attracted high interest in therapeutic development. Alzheimer's disease drugs currently used in various countries are mostly acetylcholine degrading enzyme inhibitors, such as tacrine (cognex), and donepezil (aricept). Cognex is known to be effective for patients in the early and middle stages of dementia, but side effects such as tremor, dizziness, vomiting and hepatotoxicity are known.

In addition, Bayer Pharmaceuticals also called metrifonate and END-713 from Sandoz, Forest's physostingmine SR, Astra Arcus's NXX-066 and Janssen's galanthamine also promote the synthesis of acetylcholine. Several trials have been attempted to administer the precursors, such as choline and lecithin acetylcarnitine. However, the drawback is that these substances do not cross the cerebrovascular barrier and have a short-term effect.

Therefore, in the present invention, as a result of the study to solve the problems of the side effects of the existing dementia treatment agent, the platoquinone (Plastoquinone) compound isolated from the brown algae, a marine plant inhabiting the offshore of the cholinesterase It was confirmed that there is an effect of selectively inhibiting the butylcholinesterase (BuChE) activity of the form, the formula 1 has about 300 times more potent BuChE inhibitory activity than the formula 2 and at the same time passive avoidance for ICR mice Experimental results were found to be good learning and memory to complete the present invention.

An object of the present invention is to improve cognitive abilities or improve Alzheimer's dementia by using plastoquinone compounds and their pharmaceutically acceptable salts or hydrates which are economically and efficiently isolated from brown algae, which are marine plants. It is to provide a composition.

Another object of the present invention is to provide a platoquinone compound having a selective inhibitory activity of butylcholinesterase (BuChE) in the form of cholinesterase and pharmaceutically acceptable salts or hydrates thereof. It is intended to provide a pharmaceutical composition.

Looking at the present invention in more detail as follows.

At this time, in the technical terms and scientific terms used, if there is no other definition has a meaning commonly understood by those of ordinary skill in the art. In addition, repeated description of the same technical configuration and operation as in the prior art will be omitted.

As described above, the present invention has found that the Plastoquinone compound isolated from marine edible brown algae can selectively inhibit butylcholinesterase (BuChE) activity among cholinesterase forms. As a result of measuring the terase activity, it was confirmed that the following Chemical Formula 1 had an inhibitory ability of about 300 times or more than the following Chemical Formula 2. In addition, the present invention was confirmed that the dementia improving agent comprising a Plastoquinone compound of Formula 1 and Formula 2 has an effect of improving memory and learning ability in passive avoidance experiments of ICR mice.

The present invention relates to a pharmaceutical composition containing a pharmaceutically effective amount of a platoquinone compound represented by the following Chemical Formulas 1 and 2 and their pharmaceutically acceptable salts or hydrates.

Plastoquinone compounds isolated from marine brown algae having the inhibitory ability of butylcholinesterase of the present invention are represented by the following general formula (1) or (2).

[Formula 1]

[Formula 2]

(In Formula 1, 2, R is hydrogen, alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, phenyl, phenylalkyl of 7 to 10 carbon atoms, alkanoyl of 1 to 10 carbon atoms, hydroxy phenyl or di Hydroxyphenyl group, preferably R is hydrogen.)

Further, in the present invention, the pharmaceutically acceptable base salts include ammonium salts, alkali metal salts (eg, sodium and potassium salts), alkaline earth metal salts (eg, calcium and magnesium salts) and organic bases, such as dicyclo Salts with hexylamine and N-methyl-D-glucamine).

In the present invention, the brown algae used to extract the Plastoquinone compound is Sargassum sagamianum , Eisenia bicyclis , Eisenia arborea , Ise Eisenia desmarestioides , Eisenia galapagensis , Eisenia masonii , Ecklonia kurome , Ecklonia cava , Eclonia Ecklonia stolonifera , Ecklonia maxima , Ecklonia radiata , Ecklonia bicyclis , Ecklonia biruncinate , Eclonian bushnalis Ecklonia buccinalis), Eccles Catalonia car par es Tips for (Ecklonia caepaestipes), Eccles Catalonia exciter SARS peota (Ecklonia exasperta), Eccles Catalonia Styryl starvation other (Ecklonia fastigiata), Eccles Catalonia breather bipseu (Ecklonia brevipes), Eccles Catalonia Ara beam LEA (Ecklonia arborea), Eccles Catalonia Lahti polyamic (Ecklonia latifolia), Eccles Catalonia Mura tea (Ecklonia muratii), Eccles Catalonia radio Kosa ( Ecklonia radicosa ), Ecklonia richardiana , and Ecklonia wrightii , preferably Sargassum sagamianum .

The method of extracting the plastoquinone compound from the brown algae is performed by a conventional organic solvent extraction method. The organic solvent is methanol, ethanol, ethyl acetate, acetonitrile, acetone, water, and mixtures thereof, preferably water / ethanol. Optionally, the extraction process may be repeated two or more times to increase the yield. The residues and solvents contained in the extracts are removed using conventional separation and concentrating means such as centrifuges and rotary evaporators, and may be subjected to additional separation and purification if higher purity is required, but without additional processing. The extract can be used economically advantageous.

However, the present invention is not limited to the natural material for obtaining the compound is not limited to seaweed, any natural product containing the compound can be used, it is also possible to manufacture by synthesis.

And also in the method of extracting the said compound from a natural product, if it is the method which can extract the compound of this invention, it is also possible to use an unknown method besides a well-known method.

Plastoquinone compounds of the present invention and their pharmaceutically acceptable salts or hydrates can be prepared in the form of pharmaceutical preparations and foods.

When prepared in the form of a pharmaceutical preparation in accordance with the present invention, one or two of the Plastoquinone compounds represented by the above formula (1) or (2) of the present invention are mixed and combined with a conventional carrier to provide a pharmaceutically effective amount 0.1 to 100% by weight, preferably, the dementia improving agent and the cognitive ability improving agent of the present invention may be prepared by containing 20 to 70% by weight of the pharmaceutically effective amount of the platoquinone compound.

More preferably, the Plastoquinone compound represented by Formula 1 is used in an amount of 0.1 to 6% by weight, and the Plastoquinone compound represented by Formula 2 is used in an amount of 5 to 60% by weight, and a mixture thereof. It is also possible to use. The content is a range in consideration of an effective dose of each plastoquinone compound and its pharmaceutically acceptable salt or hydrate exhibiting inhibitory activity against cholinesterase, and if the maximum total weight is exceeded, Properties may be difficult to maintain and less than the minimum weight tends to reduce the inhibitory effect of butylcholinesterase by the active ingredient.

The pharmaceutical composition comprising the platoquinone compound of the present invention and its pharmaceutically acceptable salts or hydrates as an active ingredient is prepared in all pharmaceutically acceptable forms when prepared as a medicament, And may be formulated into preparations such as injections, liquids, pills, tablets, capsules, powders, powders, chewing tablets and suspensions, preferably tablets, capsules, or liquids.

The plastoquinone compound according to the invention may be administered to a patient in any form or manner in which bioavailability is in an effective amount, ie, by oral route, depending on the nature of the disease state to be treated, the stage of the disease and other relevant circumstances. Suitable dosage forms or modes can be readily selected and the compositions according to the invention may comprise one or more pharmaceutically acceptable excipients, wherein the proportions and properties of such excipients may depend on the solubility and chemical properties of the selected tablet, It is determined by the route of administration chosen and standard drug practice.

More specifically, the compositions according to the invention may comprise a therapeutically effective amount of the above-mentioned active ingredient as an essential ingredient together with one or more pharmaceutically acceptable excipients.

Excipient materials can be solid or semisolid materials that can function as a vehicle or medium of the active ingredient, and suitable excipients are well known in the art.

Excipient materials may be selected in connection with the intended dosage form, specifically for tablets, powders, chewable tablets, granules, chewing tablets, capsules, soft capsules, pills, sublingual tablets or syrups, The therapeutically active drug component may be combined with any oral nontoxic pharmaceutically acceptable inert excipient such as lactose or starch. Optionally, the pharmaceutical tablets of the present invention may contain an amorphous cellulose, a binder such as gum tragacanth or gelatin, a disintegrant such as alginic acid, a lubricant such as magnesium stearate, a gliant such as colloidal silicon dioxide, sucrose or saccharin Flavoring agents such as peppermint or colorants or flavoring agents such as methyl salicylate.

The improving agent of the present invention is effective to ingest 1mg to 10000mg / kg, preferably 10 to 1000mg / kg daily, and the method of ingestion is not particularly limited, but oral administration is preferable.

In addition, the compounds of Formula 1 and Formula 2 are not toxic to the human body can be used as a health supplement because it can be ingested in the long term. When prepared as a dietary supplement is possible in the form included in the beverage or bakery, but is not limited thereto.

That is, when the platoquinone compound according to the present invention is dissolved with conventional sweeteners, vitamins, amino acids, minerals, organic acids, fragrances or preservatives, etc. to prepare an aqueous solution, water suspension, or a dosage form in a conventional dosage form, It can be an excellent health food that can replenish nutrients that are lacking as well as improving ability and preventing Alzheimer's dementia. Therefore, the compound of Formula 1 and Formula 2 are included as a main component, and at least one auxiliary ingredient selected from herbal extracts, vitamins, amino acids, sweeteners, minerals, organic acids, fragrances, fruit juices, or preservatives is added as necessary. In addition, it is possible to provide a novel food obtained by adding an appropriate amount of water to this and sterilizing it, or in the form of a conventional dosage form.

Auxiliary components that can be used in the present invention usually means components that can be used by those skilled in the art and are not limited thereto.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the scope of the present invention is not limited thereto.

[Production Example 1]

Preparation of Seaweed Methanol (MeOH) Extract

Seaweeds collected from offshore, Sargassum sagamianum , were first washed with distilled water to remove debris and dried in the shade before being crushed. 500 g of algae powder consisting of the algae was extracted under reflux for 2 hours in order to elute the active substance using 20 times the amount of 80% methanol. This process was repeated twice. Then, the residue was filtered off and the solvent extract was concentrated under reduced pressure using a rotary evaporator. The concentrated solution was suspended in 20 times distilled water, extracted three times using the same amount of normal hexane solvent, and the normal hexane fraction was concentrated under reduced pressure. The concentrated solution was suspended in 20-fold 30% methanol, extracted three times using the same amount of chloroform solvent, and the chloroform fraction was concentrated under reduced pressure. The concentrated solution was loaded into 15-fold reversed phase column (ODS; C18), and then subjected to reversed phase flash chromatography using 80% methanol, and concentrated by distilling out the Plastoquinone compound to prepare a crude extract. Separation and identification of the stoquinone compound represented by the following Chemical Formula 1 and Chemical Formula 2 is described in Examples 2 to 3 below.

Example 1

Choline esterase inhibitory activity was measured using the crude extract prepared in Preparation Example 1 as a sample. To measure the inhibitory activity of acetylcholinesterase, 1.0 mL of 0.1 M phosphate buffer (pH 7.3) was added to 1 mg of 1000 unit enzyme (AChE) to dissolve, and then diluted 100-fold to prepare an enzyme solution with 10 units. In this case, 0.1 mg / mL albumin (albumin) was prepared in the 10 unit enzyme. Substrate and color reagent were prepared at 5 mM, respectively. Specific methods for measuring AChE inhibitory activity are as follows.

880 μL of phosphate buffer (pH 7.3) in the cuvette, 50 μL of sample (MeOH solution), 20 μL of acetylthiocholinecholide (ATCh) with 5 mM substrate, 5,5′dithio-bis- (2-nitroben 40 μL of Zoic acid) (DTNB) were mixed and incubated at 25 ° C. for 3 minutes 40 seconds, and then 10 μL of 10 unit enzyme (AChE) solution was added thereto, and measured at 412 nm for 60 seconds. At this time, the reference value (control) should be in the range of 1.5 × 10 ⁻³ to 2.5 × 10 ⁻³ Au / sec. Measurement of the sample was added in the same volume of the sample (MeOH extract) prepared in place of MeOH, the rest using the solutions that were used as a reference value above. The butylcholinesterase inhibitory activity was also measured in the same manner as the acetylcholinesterase method. The substrate was BuTCh, and the enzyme was butylcholinesterase (BuChE). The degree of inhibitory activity is expressed in percent (%), and the percentage value is calculated as follows.

In addition, the results of the inhibition selectivity of BuChE and AChE by IC ₅₀ was calculated by the following method.

BuChE = IC ₅₀ (AChE) / IC ₅₀ (BuChE)

AChE = IC ₅₀ (BuChE) / IC ₅₀ (AChE)

As a result of measuring the inhibitory activity against cholinesterase of the extract by the same method, as shown in Table 3, the inhibition rate of crude extract was IC ₅₀ = 50 ug / ml (BuChE), IC ₅₀ = 200 ug / ml ( AChE).

[Examples 2 to 3]

Material separation was performed to identify the platoquinone compound that is a cholinesterase inhibitory substance contained in the crude extract prepared from Preparation Example 1. First, to increase the content of the platoquinone compound was loaded on silica gel, concentrated by effluent using a mixed solvent of chloroform / methanol (volume ratio 8/2), and then loaded on silica gel again, followed by chloroform / methanol (volume ratio 9/1) Using a mixed solvent of a single substance choline esterase inhibitors were separated into the following formula (1) and (2). Formula 1 is a yellow oil component, the structure was identified from the primary, secondary NMR spectrum (Table 1), the molecular formula is HRFABMS (High Resolution Fast Atom Bombardment Mass Spectrometry) spectrum [ m / z 447.2511 (M + Na) ⁺ , calcd for C ₂₇ H ₃₆ O ₄ , 447.2502] and ¹ H, ¹³ C NMR spectra showed that C ₂₇ H ₃₆ O ₄ . To been able to know the structure from the identification also the primary structure of the general formula (2), the second NMR spectra (Table 2), the aqueous phase of the general formula (2) is the oil component of the yellow color and the molecular formula is HRFABMS spectrum m / z [447.2511 (M + Na) ⁺ , calcd for C ₂₇ H ₃₆ O ₄ , 447.2502] and ¹ H, ¹³ C NMR spectra showed that C ₂₇ H ₃₆ O ₄ .

For each single substance, the inhibitory activity against cholinesterase was measured to determine the concentration showing the inhibition rate of 50%, and the IC ₅₀ was calculated. Based on the results, the selectivity was shown. These results (IC ₅₀ , selectivity) are shown in Table 3.

Table 1 NMR data of the following Chemical Formula 1 (solvent used in the analysis: CDCl ₃ - d )

Table 2 NMR data of the following Chemical Formula 2 (solvent used for analysis: CDCl ₃ - d )

[Formula 1]

[Formula 2]

[Comparative Examples 1 to 3]

IC ₅₀ was calculated by measuring the inhibitory activity against cholinesterase by using tacrine, donepezil, and pyosostigmine, which are known as representative cholinesterase inhibitors, as a control. Selectivity was shown based on the results. These results (IC ₅₀ , selectivity) are shown in Table 3.

TABLE 3 Cholinesterase inhibitory activity and selectivity

Example 4

Manual Evasion Experiments on ICR Mice

Experimental animals and drug administration: 18-20 g male mice were used. The breeding room was operated with 22 ± 1 ° C ventilation and the contrast was adjusted every 12 hours. During the breeding, water and feed were freely consumed. Example 2 (Chemical Formula 1) and Comparative Example 1 (Tacrine) in Table 3 dissolved in 5% Tween 80 as a test solution, 5% Tween80 as a control solution in the experimental group (1mg / mL group, 10mg / mL group) The test solution was administered orally to the control group once daily for 7 days. Dosing was done daily from 6:00 to 7:00 pm.

Passive avoidance conditioned response: divided into learning and testing for 2 consecutive days (interval: 24hr) at the same time. First, the learning trial was conducted 30 minutes after the last drug administration with ethanol (50% w / v) at a dose of 3 g / kg (dark adaptation), and 1 hour after the ethanol administration After 30 seconds of search time, the guillotine door was opened to allow access to the dark compartment. Rats prefer dark places, so they immediately go into the dark. Mice that did not enter the dark side within 120 seconds after opening the guillotine door were excluded from the experiment. After the guillotine door was opened, the time until the rat entered the dark side was automatically measured. Once the rat enters the dark side, the guillotine door closes and a scrambled shock flows through the grid floor, which the mouse remembers. This experiment was conducted after 6 pm. Secondly, the test was conducted 24 hours after the end of the learning trial. The latency until the rats opened the guillotine door after 30 seconds of search time and entered the dark side was measured up to 300 seconds. Longer latency indicates better learning and memory for passive avoidance. The measurement conditions are as follows.

       Measurement Condition: Exploration duration: 30 seconds

                Max Trial duration:

                  Learning-120 seconds, testing-300 seconds

                CS Light intensity: 10

                UCS Grid intensity: 0.6 ㎃

                UCS Grid duration: 5 seconds

Data processing: Student T-test was used for statistical analysis of the experimental data. The significance level was P <0.05.

[Table 4] Effects of cognition ability by repeated experiments of Formula 1

As described above, in the case of administering the platoquinone compounds of the formulas (1) and (2) according to the present invention, it was found that the selectivity to butylcholinesterase was excellent, and that the formula (1) compared to the formula (2) It was found to be excellent. In addition, as a result of administering Example 2 (Formula 1) of the present invention, it was found that the learning ability and the memory were excellent. In particular, it can be seen that as the dosage of Example 2 (Formula 1) increases, excellent learning ability and memory have good effects.

As described above, the plastoquinone compounds isolated from brown algae, which are marine plants according to the present invention, are harmless to the human body, and at the same time, they selectively inhibit only BuChE, which has recently received much interest in the form of cholinesterase. It has strong inhibitory activity, and it is expected to develop a process that can produce cholinesterase inhibitor economically, and to develop cognitive ability and functional foods and medicines for improving Alzheimer's dementia using these substances.

Claims (13)

A pharmaceutical composition for improving cognitive abilities or improving Alzheimer's dementia using a plastoquinone compound represented by the following Chemical Formula 1 or 2, and a pharmaceutically acceptable salt or hydrate thereof as an active ingredient. [Formula 1]

[Formula 2]

(In the above formula, R is hydrogen, alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, phenyl, phenylalkyl of 7 to 10 carbon atoms, alkanoyl of 1 to 10 carbon atoms, hydroxy phenyl or dihydroxyphenyl Qi.) The method of claim 1, Pharmaceutical composition for improving cognitive ability or Alzheimer's dementia, characterized in that R is hydrogen. The method of claim 1, The pharmaceutical composition for improving cognitive ability or Alzheimer's dementia, characterized in that the platoquinone compound of Formula 1 or Formula 2 and pharmaceutically acceptable salts or hydrates thereof are separated from seaweeds. The method of claim 3, wherein The seaweeds are Sargassum sagamianum , Eisenia bicyclis , Eisenia arborea , Eisenia desmarestioides , and Iceenia galapazennis . ( Eisenia galapagensis ), Eisenia masonii , Ecklonia kurome , Ecklonia cava , Ecklonia stolonifera , Ecklonia maxima , Eclonia radiata , eclonia bicyclis , eclonia biruncinate , eclonia buccinalis , eclonia caepaestipes , Eccles Catalonia exciter SARS peota (Ecklonia exasperta), Eccles Catalonia parse tee starvation other (Ecklonia fastigiata), Eccles Catalonia breather bipseu (Ecklonia brevipes), the Catalonia Ara beam LEA (Ecklonia arborea), Eccles Catalonia Lahti polyamic (Ecklonia latifolia), Eccles Catalonia Mura tea (Ecklonia muratii), Eccles Catalonia radio Kosa (Ecklonia radicosa), Eccles Catalonia retarder Diana (Ecklonia richardiana) and Eccles Catalonia La ET ( Ecklonia wrightii ) pharmaceutical composition for improving cognitive ability or Alzheimer's dementia, characterized in that any one or more selected from. The method according to any one of claims 1 to 4, Pharmaceutical composition for improving cognitive ability or Alzheimer's dementia, characterized in that it contains 0.1 to 100% by weight of any one or more compounds selected from Formula 1 or Formula 2 and their pharmaceutically acceptable salts or hydrates. The method of claim 5, Improving cognitive ability, characterized in that it contains 0.1 to 6% by weight of the plastoquinone compound represented by the formula (1), 5 to 60% by weight of the platoquinone compound (Plastoquinone) represented by the formula (2) or a mixture thereof Or Alzheimer's dementia improvement pharmaceutical composition. The method of claim 5, Pharmaceutical composition for improving cognitive ability or Alzheimer's dementia, characterized in that any one selected from the form of injections, liquids, pills, tablets, capsules, powders, powders, chewing tablets and suspensions. The method of claim 5, Pharmaceutical composition for improving cognitive ability or Alzheimer's dementia, characterized in that the daily intake amount of 1 to 10000mg / kg based on the active ingredient. A dietary supplement comprising at least one plastoquinone compound represented by Formula 1 or 2 below. [Formula 1]

[Formula 2]

(In the above formula, R is hydrogen, alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, phenyl, phenylalkyl of 7 to 10 carbon atoms, alkanoyl of 1 to 10 carbon atoms, hydroxy phenyl or dihydroxyphenyl Qi.) The method of claim 9, The plastoquinone compound of Formula 1 or Formula 2 is a health supplement, characterized in that separated from the algae. The method of claim 10, The seaweeds are Sargassum sagamianum , Eisenia bicyclis , Eisenia arborea , Eisenia desmarestioides , and Iceenia galapazennis . ( Eisenia galapagensis ), Eisenia masonii , Ecklonia kurome , Ecklonia cava , Ecklonia stolonifera , Ecklonia maxima , Eclonia radiata , eclonia bicyclis , eclonia biruncinate , eclonia buccinalis , eclonia caepaestipes , Eccles Catalonia exciter SARS peota (Ecklonia exasperta), Eccles Catalonia parse tee starvation other (Ecklonia fastigiata), Eccles Catalonia breather bipseu (Ecklonia brevipes), the Catalonia Ara beam LEA (Ecklonia arborea), Eccles Catalonia Lahti polyamic (Ecklonia latifolia), Eccles Catalonia Mura tea (Ecklonia muratii), Eccles Catalonia radio Kosa (Ecklonia radicosa), Eccles Catalonia Rica Diana (Ecklonia richardiana) and Eccles Catalonia La ET ( Ecklonia wrightii ) dietary supplement, characterized in that at least one selected from. The method according to any one of claims 9 to 10, The food is a health supplement food, characterized in that the beverage or bakery. A pharmaceutical composition for the selective inhibitory activity of butylcholinesterase containing the platoquinone compounds of formulas (1) and (2). [Formula 1]

[Formula 2]

(In the above formula, R is hydrogen, alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, phenyl, phenylalkyl of 7 to 10 carbon atoms, alkanoyl of 1 to 10 carbon atoms, hydroxy phenyl or dihydroxyphenyl group to be.)

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