KR20230138688A - Pharmaceutical composition for preventing or treating diseases caused by beta-amyloid aggregation containing halenaquinol sulfate as an active ingredient - Google Patents

Abstract

The purpose of the present invention is to provide a pharmaceutical composition for preventing or treating diseases caused by beta-amyloid aggregation containing Halenaquinol sulfate as an active ingredient. Halenaquinol sulfate of the present invention inhibits the aggregation of beta-amyloid in a concentration-dependent manner and It has the effect of decomposing amyloid aggregates, and has been confirmed to have an inhibitory effect on Acetylcholinesterase and an effect on improving the inhibition of synaptic plasticity (LTP) by beta-amyloid, so that diseases caused by beta-amyloid aggregation can be prevented and treated, so it is a useful business related to this. can be used

Description

Pharmaceutical composition for preventing or treating diseases caused by beta-amyloid aggregation containing halenaquinol sulfate as an active ingredient}

The purpose of the present invention is to provide a pharmaceutical composition for preventing or treating diseases caused by beta-amyloid aggregation containing Halenaquinol sulfate as an active ingredient.

Amyloid plaques are a mass structure of condensed proteins found on the outside of neurons in the brains of Alzheimer's patients. Amyloid plaques are caused by misfolding of multimers of beta-amyloid protein (Aβ). Once a misfolded amyloid multimer has a negative effect on new Aβ, it also induces the protein structure of the newly created amyloid multimer to be misfolded. Amyloid plaques are formed when this phenomenon spreads. Controversy continues as to whether amyloid plaques are the direct cause of Alzheimer's disease. In a study on mice created by manipulating the gene for the enzyme involved in Aβ production, the incidence of Alzheimer's disease in mice forming amyloid multimers was significantly higher than in mice forming amyloid plaques. This is interpreted that amyloid multimers are a more direct cause of Alzheimer's disease than amyloid plaques. However, since the pathogenesis of Alzheimer's disease involves several proteins, such as tau and alpha-synuclein, in addition to Aβ, more detailed research should be conducted on these proteins.

Aβ is a protein that is the main component of amyloid plaques and is closely related to Alzheimer's disease. Aβ is produced from amyloid precursor protein (APP) embedded in the plasma membrane. Beta secretase and gamma secretase sequentially recognize specific amino acid sequences of APP and break the peptide bond, producing Aβ consisting of 36-43 amino acids. Aβ molecules form various types of multimers through the protein aggregation process. These multimers have biochemical characteristics such as high water solubility and elasticity. However, during the formation of multimers, errors occur in the folding of proteins, and these misfolded multimers affect the process of Aβ molecules forming new multimers, leading to misfolding of the multimers. In other words, once a misfolded Aβ multimer spreads the process of continuously misfolding multimers. Therefore, protein folding of Aβ multimers is believed to play a critical role in the process of forming amyloid plaques.

As average lifespan increases, the incidence of degenerative brain diseases is increasing significantly. In particular, senile dementia, including Alzheimer's disease, is recognized as a disease that is accompanied by functional disorders that result in an abnormal decline in overall cognitive and higher mental functions such as language, learning, and intelligence, which increases the burden not only on the patient but also on those around him. Although many target mechanisms have been discovered, there are still only drugs used for dementia, including Alzheimer's disease, that are expected to slow the progression of the disease by blocking NMDA receptors and acetylcholine degrading enzyme inhibitors that can increase the amount of acetylcholine in the brain. . In addition, the efficacy of these medicines is low and they are merely symptom improvers rather than disease treatments.

Accordingly, while researching beta-amyloid aggregation, a substance that causes degenerative brain diseases, the present inventors confirmed that Halenaquinol sulfate and its salt of the present invention inhibit beta-amyloid aggregation and decompose the aggregates, thereby completing the present invention.

The purpose of the present invention is to provide a food composition for preventing and improving diseases caused by beta-amyloid aggregation containing Halenaquinol sulfate and its salt as an active ingredient.

Additionally, an object of the present invention is to provide a pharmaceutical composition for the prevention and treatment of diseases caused by beta-amyloid aggregation, containing Halenaquinol sulfate and its salt as an active ingredient.

In addition, the purpose of the present invention is to provide a food composition for improving memory containing Halenaquinol sulfate and its salt as an active ingredient.

The present invention provides a food composition for preventing and improving diseases caused by beta-amyloid aggregation, comprising Halenaquinol sulfate and its salt as an active ingredient.

Additionally, the present invention provides a pharmaceutical composition for preventing and treating diseases caused by beta-amyloid aggregation, comprising Halenaquinol sulfate and its salt as an active ingredient.

In addition, the present invention provides a food composition for improving memory containing Halenaquinol sulfate and its salt as an active ingredient.

Halenaquinol sulfate of the invention has the effect of suppressing the aggregation of beta-amyloid in a concentration-dependent manner, decomposing beta-amyloid aggregates, and improving the inhibitory effect of acetylcholinesterase and the inhibition of synaptic plasticity (LTP) by beta-amyloid. Because it can prevent and treat diseases caused by agglutination, it can be used in useful projects related to this.

Figure 1 is a diagram showing the chemical structure of Halenaquinol sulfate.
Figure 2 is a diagram showing the inhibitory effect of beta-amyloid aggregation at different concentrations of Halenaquinol sulfate. Curcumin was used as a positive control.
Figure 3 is a diagram showing the effect of halenaquinol sulfate in decomposing beta-amyloid aggregates at different concentrations. Curcumin was used as a positive control.
Figure 4 is a diagram showing the inhibitory effect of acetylcholinesterase at different concentrations of Halenaquinol sulfate.
Figure 5 is a diagram showing the effect of Halenaquinol sulfate on improving synaptic plasticity (LTP) inhibition caused by beta-amyloid.

Hereinafter, the present invention will be described in detail through embodiments of the present invention with reference to the attached drawings. However, the following embodiments are provided as examples of the present invention, and if it is judged that a detailed description of a technology or configuration well known to those skilled in the art may unnecessarily obscure the gist of the present invention, the detailed description may be omitted. , the present invention is not limited by this, and the present invention is capable of various modifications and applications within the description of the claims described later and the scope of equivalents interpreted therefrom.

In addition, the terminology used in this specification is a term used to appropriately express preferred embodiments of the present invention, and may vary depending on the intention of the user or operator or the customs of the field to which the present invention belongs. Therefore, definitions of these terms should be made based on the content throughout this specification. Throughout the specification, when a part is said to “include” a certain element, this means that it may further include other elements rather than excluding other elements, unless specifically stated to the contrary.

All technical terms used in the present invention, unless otherwise defined, are used with the same meaning as commonly understood by a person skilled in the art in the field related to the present invention. In addition, preferred methods and feeds are described in this specification, but similar or equivalent methods are also included in the scope of the present invention. The contents of all publications incorporated by reference herein are hereby incorporated by reference.

The present invention provides a food composition for preventing and improving diseases caused by beta-amyloid aggregation, comprising Halenaquinol sulfate and its salt as an active ingredient.

The term “prevention” used in the present invention refers to any action that suppresses the symptoms or delays the progression of a specific disease by administering the composition of the present invention.

As used herein, the term “improvement” refers to any action that reduces at least the severity of a parameter, such as a symptom, related to the condition being treated.

The Halenaquinol sulfate is represented by the following formula (1), but is not limited thereto.

[Formula 1]

The salt acceptable for the food composition or pharmaceutical composition may include an acid addition salt formed by a pharmaceutically acceptable free acid, and the free acid may be an organic acid or an inorganic acid. The organic acids include citric acid, acetic acid, lactic acid, tartaric acid, maleic acid, fumaric acid, formic acid, propionic acid, oxalic acid, trifluoroacetic acid, benzoic acid, gluconic acid, metasulfonic acid, glycolic acid, succinic acid, 4-toluenesulfonic acid, glutamic acid, aspartic acid, etc. It may include, but is not limited to this. Additionally, the inorganic acid may include hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, etc., but is not limited thereto.

Halenaquinol sulfate inhibits beta-amyloid aggregation, but is not limited thereto.

Halenaquinol sulfate decomposes beta-amyloid aggregates, but is not limited thereto.

The Halenaquinol sulfate improves synaptic plasticity (LTP) inhibition caused by beta-amyloid, but is not limited thereto.

Halenaquinol sulfate inhibits acetylcholinesterase, but is not limited thereto.

The disease caused by beta-amyloid aggregation is one or more from the group consisting of Alzheimer's dementia, Down syndrome, amyloid angiopathy, systemic amyloid disease, Dutch amyloidosis, or inclusion body stomatitis, but is not limited thereto.

The Halenaquinol sulfate is obtained from the sponge Xestospongia sp. , but is not limited thereto.

The present invention provides a pharmaceutical composition for preventing and treating diseases caused by beta-amyloid aggregation, comprising Halenaquinol sulfate and its salt as an active ingredient.

The term “treatment” used in the present invention refers to any action that improves or beneficially changes the symptoms of a specific disease by administering the composition of the present invention.

The present invention provides a composition for improving memory containing Halenaquinol sulfate and its salt as active ingredients.

The main component of neurula, which is the main feature of the brain of Alzheimer's disease patients, is insoluble Aβ aggregates, but soluble Aβ oligomers present in the extracellular space have recently been shown to be closely related to cognitive decline and disease progression in Alzheimer's disease animal models and patients. It is being brought in. Much evidence has shown that Aβ oligomers, especially Aβ1-42 oligomers, directly affect synaptic plasticity and cause loss of synaptic dendritic spines.

When the Aβ1-40 oligomer is formed into a tetramer, no more Aβ binds, so the tetramer reaches its maximum size, whereas for Aβ1-42, an “open” tetramer is formed and the formation of a planar hexamer (paranucleus) is promoted, leading to the formation of a demer. .

It was reported that soluble Aβ dimer extracted directly from the cerebral cortex of Alzheimer's disease patients inhibited long-term potentiation (LTP), enhanced long-term depression (LTD), and reduced dendritic spines in the normal mouse hippocampus.

In addition to containing the active ingredient, the food composition of the present invention may contain various flavoring agents or natural carbohydrates as additional ingredients like a normal food composition.

Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose, etc.; Disaccharides such as maltose, sucrose, etc.; and polysaccharides, such as common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. The above-described flavoring agents include natural flavoring agents (thaumatin), stevia extracts (e.g. rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.). The food composition of the present invention can be formulated in the same way as the pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, meat, chocolate, foods, confectionery, pizza, ramen, other noodles, gum, candy, ice cream, alcoholic beverages, vitamin complexes, health supplements, etc. There is.

In addition to the extract as an active ingredient, the food composition contains various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavors, colorants and thickening agents (cheese, chocolate, etc.), pectic acid and its salts, It may contain alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. In addition, the food composition of the present invention may contain pulp for the production of natural fruit juice, fruit juice beverages, and vegetable beverages.

The functional food composition of the present invention can be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. In the present invention, 'health functional food composition' refers to food manufactured and processed using raw materials or ingredients with functionality useful to the human body in accordance with Act No. 6727 on Health Functional Food, and refers to food that is related to the structure and function of the human body. It means taking it for the purpose of controlling nutrients or obtaining useful health effects such as physiological effects. The health functional food of the present invention may contain common food additives, and its suitability as a food additive is determined in accordance with the general provisions and general test methods of the food additive code approved by the Food and Drug Administration, unless otherwise specified. Judgment is made according to specifications and standards. Items listed in the 'Food Additive Code' include, for example, chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; Natural additives such as dark pigment, licorice extract, crystalline cellulose, kaoliang pigment, and guar gum; Examples include mixed preparations such as sodium L-glutamate preparations, noodle additive alkaline preparations, preservative preparations, and tar coloring preparations. For example, the health functional food in the form of a tablet is made by granulating a mixture of the active ingredient of the present invention with excipients, binders, disintegrants and other additives in a conventional manner, and then adding a lubricant and compression molding, or The mixture can be directly compression molded. Additionally, the health functional food in the form of tablets may contain flavoring agents, etc., if necessary. Among capsule-type health functional foods, hard capsules can be manufactured by filling a regular hard capsule with a mixture of the active ingredient of the present invention mixed with additives such as excipients, and soft capsules can be prepared by mixing the active ingredient of the present invention with additives such as excipients. It can be manufactured by filling the mixture with a capsule base such as gelatin. The soft capsule may contain plasticizers such as glycerin or sorbitol, colorants, preservatives, etc., if necessary. The health functional food in the form of a pill can be prepared by molding a mixture of the active ingredient of the present invention and excipients, binders, disintegrants, etc., using a known method. If necessary, it can be coated with white sugar or other coating agent. Alternatively, the surface can be coated with substances such as starch or talc. Health functional food in the form of granules can be manufactured into granules by mixing a mixture of excipients, binders, disintegrants, etc. of the active ingredients of the present invention by a known method, and may contain flavoring agents, flavoring agents, etc., if necessary. You can.

The pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier. In the present invention, the term “pharmaceutically acceptable” means that the composition exhibits non-toxic properties to cells or humans exposed to the composition. The carrier may be used without limitation as long as it is known in the art, such as a buffer, preservative, analgesic agent, solubilizer, isotonic agent, stabilizer, base, excipient, lubricant, etc.

In addition, the pharmaceutical composition of the present invention can be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injection solutions according to conventional methods. You can. Furthermore, it can be used in the form of an ointment, lotion, spray, patch, cream, powder, suspension, gel, or external skin preparation in the form of a gel. Carriers, excipients and diluents that may be included in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations include the Cycotria rubra extract with at least one excipient, such as starch, calcium carbonate, It is prepared by mixing sucrose, lactose, and gelatin. In addition to simple excipients, lubricants such as magnesium styrate and talc are also used. Liquid preparations for oral use include suspensions, oral solutions, emulsions, and syrups. In addition to the commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. there is. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. As a base for suppositories, witepsol, macrogol, tween 61, cacao, laurin, glycerogeratin, etc. can be used.

The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. The term "administration" in the present invention means introducing a predetermined substance into an individual by an appropriate method, and the composition may be administered through any general route as long as it can reach the target tissue. It may be administered intraperitoneally, intravenously, intramuscularly, subcutaneously, intradermally, orally, topically, intranasally, intrapulmonaryly, or rectally, but is not limited thereto.

Hereinafter, the present invention will be described in more detail through the following examples. However, the following examples are only examples to easily explain the content and scope of the technical idea of the present invention, and the technical scope of the present invention is not limited or changed thereby. Additionally, based on these examples, it can be easily determined by those skilled in the art that various modifications and changes are possible within the scope of the technical idea of the present invention.

[Example]

Example 1. Drugs and Reagents

Beta-amyloid 1-42 was purchased from Anaspec. Halenaquinol sulfate was isolated and provided by the inventor, Dr. Heeseung Lee of the Korea Institute of Ocean Science and Technology. Other reagents were of the highest quality commercially available. In order to obtain the halenaquinol sulfate compound with anti-amyloid activity of the present invention, specifically, samples of the sponge Xestospongia sp. were collected from a water depth of 15 to 20 m in Weno Island, Chuuk, Micronesia. was obtained and frozen, then extracted repeatedly with methanol and dichloromethane, filtered, and depressurized to obtain a crude extract.

Afterwards, the crude extract was fractionated into water and butanol to obtain organic matter from the butanol layer, and then re-fractionated into methanol and hexane mixed with 15% water to obtain polar organic matter from the methanol layer. The polar organics were subjected to C18 reverse-phase chromatography to obtain a mixture of fractions eluted with MeOH-H ₂ O (1:1) solvent, which were then subjected to HPLC (YMC-ODS column, 10 mm x 250 mm; MeOH-H ₂ O, 35:65), the halenaquinol sulfate compound was isolated. The structural formula of the compound is shown in Figure 1.

Example 2. Statistical processing

Statistical analysis and graphs used in the experiments of the present invention used Graphpad Prism 5.0. A t-test was used to compare two groups, and one-way analysis of variance (ANOVA) was used to compare three or more groups. When significance was found through ANOVA analysis, each group was compared using post-hoc Turkey’s pairwise comparison, and it was recognized as statistically significant in the range of p < 0.05.

Example 3. Halenaquinol sulfate compound inhibits beta-amyloid aggregation and decomposes aggregates.

Halenaquinol sulfate compound To confirm the effect of inhibiting beta-amyloid (Aβ) aggregation and decomposing beta-amyloid (Aβ) aggregates, a method was used to confirm the degree of protein aggregation in vitro. Thioflavin T (ThT), a benzothiazole dye, was purchased from Sigma (T3516) and dissolved in DPBS. Amyloid β 1-42 (Aβ42) protein was dissolved in DMSO at 1 mM and diluted with DPBS to 100 μM. Halenaquinol sulfate was used dissolved in DMSO. To check the degree of Aβ42 aggregation, the amounts of Aβ42 and halenaquinol sulfate were mixed 1:1 and placed in a black Eppendorf tube and incubated at 37°C for 24 hours. The final concentrations used were Aβ42 (10 μM), halenaquinol sulfate (10 μM), curcumin (10 μM), and ThT (45 μM). 100 μl/well was placed in a 96-well black plate, and fluorescence values were measured at 485 nm / 528 nm wavelengths using a Synergy™ HTX multi-mode microplate reader. All procedures were performed three times.

After culturing beta-amyloid (Aβ) 42 for 24 hours, the amounts of beta-amyloid (Aβ) 42 and halenaquinol sulfate were mixed 1:1, placed in a black Eppendorf tube, and incubated for an additional 24 hours at 37 °C. The final concentrations used were Aβ42 (10 μM), halenaquinol sulfate (10 μM), curcumin (10 μM), and ThT (45 μM). 100 μl/well was placed in a 96-well black plate, and fluorescence values were measured at 485 nm / 528 nm wavelengths using a Synergy™ HTX multi-mode microplate reader. All procedures were performed three times.

Example 3-1. Halenaquinol sulfate compound inhibits beta-amyloid aggregation.

According to Example 3, when only beta-amyloid was cultured, the magnitude of the fluorescence intensity was set to 100 to test whether aggregation of halenaquinol sulfate and curcumin (positive control) could be inhibited.

As a result, Halenaquinol sulfate was confirmed to have inhibitory activity against aggregation of beta-amyloid (10 μM) in a concentration-dependent manner (Figure 2).

Example 3-2. Halenaquinol sulfate compound decomposes beta-amyloid aggregates

According to Example 3, beta-amyloid was cultured for 24 hours to form aggregates, and then halenaquinol sulfate was added to test whether the already aggregated beta-amyloid aggregates could be decomposed.

As a result, it was confirmed that Halenaquinol sulfate decomposes already aggregated beta-amyloid aggregates in a concentration-dependent manner (Figure 3).

Example 4. Inhibition of Acetylcholinesterase (AChE) with Halenaquinol sulfate Compound active measurement

To confirm the inhibitory activity of Acetylcholinesterase (AChE) with a halenaquinol sulfate compound, the enzymatic activity of Acetylcolinerase (AChE) was tested using acetylthiocholine as a substrate according to the Ellman method (Ellman et al., 1961), and thiocholine produced by AChE was mixed with DTNB. The reaction was performed by measuring the change in absorbance of the resulting 5-thio-2-nitrobenzoate at 405 nm. To a 96 well microplate, 100 μL of AChE assay buffer (0.1 M Tris-HCl, pH 8.2), 10 μL of 0.5 U/ml AChE (dissolved in assay buffer containing 10% glycerol), and 10 μL of appropriately diluted sample were added. After incubation for 10 minutes at room temperature while shaking, 10 μL of 10 mM DTNB and 5 μL of 100 mM acetylthiocholine were added, reacted for 2 minutes, and then incubated for 2 minutes using a microplate reader (Spectramax PLUS 384, Molecular Device, USA). Absorbance was measured in nm. At this time, the same amount of assay buffer was added instead of enzyme as a control. Inhibitory activity by AChE inhibitor was calculated using the following formula.

Inhibition rate (%) = 100-(As/Ac)×100

At this time, Ac is the absorbance of the control group, and As is the absorbance of the sample group.

As a result, Halenaquinol sulfate inhibited acetylcholinesterase activity in a concentration-dependent manner, and the IC50 was confirmed to be 17.85 μM (Figure 4).

Example 5. Effect of Halenaquinol sulfate on improving inhibition of synaptic plasticity (LTP) by beta-amyloid

An experiment was conducted to confirm that Halenaquinol sulfate significantly improved the inhibition of synaptic plasticity (LTP) by beta-amyloid compared to the control group.

5-1 Electrophysiology

The hippocampus of an ICR mouse (26-28, 6 weeks old, male, Samtaco) was removed, 300 micrometer-thick sections were prepared, and infused with artificial cerebrospinal fluid (NaCl, 124 mM; KCl, 3 mM; NaHCO3, 26 mM; NaH2PO4, 1.6 mM; CaCl2, 2mM; MgSO4, 2mM; d-glucose, 10mM) for 2 hours. Afterwards, the brain tissue was placed in a recording chamber where artificial cerebrospinal fluid flows at a rate of 2 ml/sec, a stimulating electrode was placed in CA3, a recording electrode was placed in the Schaffer-collaterla pathway, and stimulation was applied once every 30 seconds to measure the response. After measuring the baseline for 20 minutes, high frequency stimulation (HFS, 100 pulses for 100 seconds) was applied, and responses were measured by stimulating once every 30 seconds for the next 60 minutes. Hippocampal slices were incubated in a solution of halenaquinol sulfate (10 μM) for 30 minutes before the experiment, and then incubated for 2 hours in a solution containing oligomeric beta-amyloid (1 μM) and halenaquinol sulfate (10 μM).

As a result, oligomeric beta-amyloid significantly reduced synaptic long-term potentiation (LTP), a cellular model of memory, compared to the control group, and halenaquinol sulfate was confirmed to significantly inhibit the effect of beta-amyloid (Figure 5).

So far, the present invention has been examined focusing on its preferred embodiments. A person skilled in the art to which the present invention pertains will understand that the present invention may be implemented in a modified form without departing from the essential characteristics of the present invention. Therefore, the disclosed embodiments should be considered from an illustrative rather than a restrictive perspective. The scope of the present invention is indicated in the claims rather than the foregoing description, and all differences within the equivalent scope should be construed as being included in the present invention.

Claims (11)

A food composition for preventing and improving diseases caused by beta-amyloid aggregation, containing halenaquinol sulfate and its salt as active ingredients. According to clause 1,
The Halenaquinol sulfate is a composition represented by the following formula (1):
[Formula 1]
According to clause 1,
A composition wherein the Halenaquinol sulfate inhibits beta-amyloid aggregation. According to clause 1,
A composition wherein the Halenaquinol sulfate decomposes beta-amyloid aggregates. According to clause 1,
A composition in which the Halenaquinol sulfate improves the inhibition of synaptic plasticity (LTP) by beta-amyloid. According to clause 1,
A composition wherein the Halenaquinol sulfate inhibits acetylcholinesterase. According to clause 1,
The composition, wherein the disease caused by beta-amyloid aggregation is at least one from the group consisting of Alzheimer's dementia, Down syndrome, amyloid angiopathy, systemic amyloid disease, Dutch amyloidosis, or inclusion body stomatitis. According to clause 1,
The composition wherein the Halenaquinol sulfate is obtained from the sponge Xestospongia sp . A pharmaceutical composition for the prevention and treatment of diseases caused by beta-amyloid aggregation, containing halenaquinol sulfate and its salt as active ingredients. According to clause 9,
The composition, wherein the disease caused by beta-amyloid aggregation is at least one from the group consisting of Alzheimer's dementia, Down syndrome, amyloid angiopathy, systemic amyloid disease, Dutch amyloidosis, or inclusion body stomatitis. A composition for improving memory containing halenaquinol sulfate and its salt as active ingredients.