KR101887178B1 - A composition comprising extract of rhei undulatai rhizoma for preventing or treating neurodegenerative disease and stress disease - Google Patents

Abstract

The present invention provides a composition comprising an extract of Rhei Undulatai Rhizoma as an effective component for preventing or treating degenerative brain diseases.

Description

TECHNICAL FIELD [0001] The present invention relates to a composition for preventing or treating a degenerative brain disease containing an extract of Rhododendron sulphate as an active ingredient,

The present invention relates to a composition for the prevention or treatment of degenerative brain diseases containing an extract of spermatogonia as an active ingredient.

In recent years, concerns about neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease have increased rapidly.

Regarding such degenerative brain diseases, there are no fundamental therapeutic agents to date, and even therapeutic agents that temporarily inhibit the progression of the disease have a limitation due to a decrease in the drug efficacy and various side effects due to the worsening of the disease.

On the other hand, herbal medicines mainly used in Oriental medicine are becoming more fundamental therapeutic agents by multi-target mechanism in the prevention and treatment of chronic and intractable diseases in which causes and symptoms are complex.

In addition, therapeutic agents using such herbal medicines as raw materials are attracting attention as substitutes for existing pharmaceutical ingredients because they can minimize various side effects that may occur depending on the use of chemicals (KR 10-2011-0108150 A , KR 10-2009-0078939 A).

Disclosure of Invention Technical Problem [8] Accordingly, the present invention has been made to solve the above problems occurring in the prior art, and it is an object of the present invention to provide a composition containing a herbal medicine component derived from a natural product to minimize side effects and to improve degenerative brain diseases.

One aspect of the present invention relates to a method for the treatment of rheumatoid arthritis Undulatai Rhizoma extract as an active ingredient. The present invention also provides a pharmaceutical composition for preventing or treating degenerative brain diseases.

In one embodiment, the bovine rhubarb extract may be extracted with water, a C ₁ -C ₄ lower alcohol, or a mixed solvent thereof.

In one embodiment, the lower alcohol may be ethanol.

In one embodiment, the degenerative brain disease is selected from the group consisting of dementia, Alzheimer's disease, stroke, cerebral infarct, head trauma, cerebral arteriosclerosis, Parkinson ' s disease. ≪ / RTI >

It is another aspect of the present invention are species of rhubarb (Rhei Undulatai Rhizoma ) extract as an active ingredient for the prevention or treatment of degenerative brain diseases.

Another aspect of the present invention relates to a method of preparing a compound of formula Undulatai Rhizoma ) extract as an active ingredient.

Another aspect of the present invention relates to a method of treating rheumatoid arthritis, Undulatai Rhizoma ) extract as an active ingredient.

According to one aspect of the present invention, it is possible to improve the effect of improving the degenerative brain disease while minimizing adverse effects by using a medicinal composition or a medicinal herb extract, which is a natural herbal medicine, as a component of a health functional food.

It should be understood that the effects of the present invention are not limited to the effects described above, but include all effects that can be deduced from the description of the invention or the composition of the invention set forth in the claims.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a graph showing the inhibitory effect of amyloid-beta agglutination of a sardine extract according to an embodiment of the present invention.
FIG. 2 is a graph showing the neuroprotective effect of the extract of the rhubarb extract according to an embodiment of the present invention. FIG.
FIG. 3 and FIG. 4 are graphs showing the anti-inflammatory activity of the bovine rhubarb extract according to an embodiment of the present invention.

As used herein, the terminology used herein is intended to encompass all commonly used generic terms that may be considered while considering the functionality of the present invention, but this may vary depending upon the intent or circumstance of the skilled artisan, the emergence of new technology, and the like. Also, in certain cases, there may be a term selected arbitrarily by the applicant, in which case the meaning thereof will be described in detail in the description of the corresponding invention. Therefore, the term used in the present invention should be defined based on the meaning of the term, not on the name of a simple term, but on the entire contents of the present invention.

Unless defined otherwise, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Terms such as those defined in commonly used dictionaries are to be interpreted as having a meaning consistent with the contextual meaning of the related art and are to be interpreted as either ideal or overly formal in the sense of the present application Do not.

The numerical range includes numerical values defined in the above range. All numerical limitations of all the maximum numerical values given throughout this specification include all lower numerical limitations as the lower numerical limitations are explicitly stated. All the minimum numerical limitations given throughout this specification include all higher numerical limitations as the higher numerical limitations are explicitly stated. All numerical limitations given throughout this specification will include any better numerical range within a broader numerical range, as narrower numerical limitations are explicitly stated.

Hereinafter, embodiments of the present invention will be described in detail, but it should be apparent that the present invention is not limited by the following examples.

Prevention or treatment a pharmaceutical composition for neurodegenerative disease according to one aspect of the present invention, two kinds of rhubarb (Rhei Undulatai Rhizoma ) extract as an active ingredient.

The term " neurodegenerative disease " refers to a disease occurring in the brain, among neurodegenerative diseases caused by age. Although the cause of the disease has not been clearly identified, the specific brain cell group of the brain and spinal cord has gradually lost its function, and the death of neuronal cells, which play a key role in the transmission of the brain nervous system, The formation and functioning of the brain, and the ideal increase and decrease of the brain nerve potential. The degenerative brain disease can be classified according to the major symptom and the damaged area of the brain, and typical examples thereof include Alzheimer's disease and Parkinson's disease.

The " Rhei Undulatai Rhizoma) "is a kind of rhubarb (Rheum undulatum to refer to the rootstock of Linne), usually kind of rhubarb that name is the concept that means Latin saengyakmyeong Rhei Undulatai Rhizoma of Rheum undulatum Linne, not, rhizomes, which refers to the scientific names belonging to knotgrass .

The "rhizome" refers to a special form of a stem that has a root shape and extends to the ground. These rhizomes function as a root-like function, that is, means of reproduction of nutrition, so that they can contain a large amount of various active ingredients.

The major sulfur contains a large amount of anthraquinone derivatives such as emodin and aloeemodin, and it is known to have an effect such as the action of the matrix, the sub-action, the antibacterial action, and the anti-tumor action. It has also been reported that the above-mentioned emodin exhibits 100% blood vessel relaxation response to the 5-hydroxytriptamine-induced maximal contraction reaction in the thoracic aorta and shows excellent efficacy as a therapeutic agent for vascular diseases .

However, to date, there have been no reports on the action mechanism or efficacy of the species of rhubarb in relation to the improvement of degenerative brain diseases such as Alzheimer's disease and Parkinson's disease.

Unlike the artificial compound, the sardine-derived sulfur extract uses the substance derived from a natural product as it is, so that it is possible to minimize the occurrence of fatal side effects due to ingestion or administration thereof.

On the other hand, the type of solvent in the extraction process is not particularly limited, and various solvents may be used as needed. In addition, the extraction can be carried out using a conventional method in the art such as cold-rolling, warming, heating, and the like using the solvent.

Accordingly, the sardine-extract can be extracted with water, a C ₁ -C ₄ lower alcohol, or a mixed solvent thereof. Preferably, ethanol, more preferably 70% ethanol, can be used. However, It is not.

When ethanol is used as the extraction solvent, not only the stability can be enhanced but also it is harmless to the human body. Therefore, it can exhibit excellent suitability for use as a food or pharmaceutical composition, and the cost increase such as strict process control for securing stability It is possible to improve the economic effect.

The composition may further comprise carriers, excipients and diluents used in the preparation of conventional pharmaceutical compositions.

Examples of the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, But are not limited to, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil.

In addition, the composition may be formulated in the form of oral, granule, tablet, capsule, suspension, emulsion, syrup, aerosol or the like, external preparation, suppository and sterilized injection solution.

The solid preparations for oral administration include tablets, pills, powders, granules, capsules and the like. These solid preparations may contain at least one excipient such as starch, calcium carbonate, sucrose, Lactose, or gelatin. In addition to the above excipients, lubricants such as magnesium stearate and talc may also be used.

Examples of the liquid preparation for oral administration include suspensions, solutions, emulsions, syrups, and the like. In addition to water and liquid paraffin, simple diluents, various excipients such as wetting agents, sweeteners, have.

The preparation for parenteral administration may be a sterilized aqueous solution, a non-aqueous solvent, a suspension, an emulsion, a lyophilized preparation, or a suppository. Examples of the non-aqueous solvent and suspensions may include injectable esters such as propylene glycol, polyethylene glycol, vegetable oil such as olive oil and ethyl oleate. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, and glycerogelatin.

A pharmaceutical composition comprising said sardine-extract can be administered to a subject in a pharmaceutically effective amount. The " pharmaceutically effective amount " means an amount sufficient to treat the disease at a reasonable benefit / risk ratio applicable to the medical treatment, and the effective dosage level will depend on the type of disease, severity, activity of the drug, Sensitivity, time of administration, route of administration and rate of excretion, duration of treatment, factors including co-administered drugs, and other factors well known in the medical arts.

The pharmaceutical composition may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or in multiple doses. It is desirable to administer an amount that allows for all of the above factors to be maximally effected in a minimal amount without side effects, which can be readily determined by one skilled in the art.

Another aspect of the present invention relates to a method of treating rheumatoid arthritis, Undulatai Rhizoma ) extract as an active ingredient for the prevention or treatment of degenerative brain diseases.

That is, the composition may be a food composition as well as a pharmaceutical composition. In this case, the food may be meat, snacks, dairy products, beverages, and the like, but the present invention is not limited thereto, and may be understood as including all conventional health functional foods.

The health functional food refers to a food prepared and processed by using a raw material or a component having a useful function in the human body according to the Health Functional Food Act No. 6727. The functional property refers to the nutrient Or for the purpose of obtaining a beneficial effect for health use such as physiological action.

The above-mentioned health functional foods may contain usual food additives, and the above food additives may be added to the standards and standards of the relevant items in accordance with the General Rules for Food Additives approved by the Food and Drug Administration and the General Test Methods, It can be judged whether it is suitable or not. The food additives described in the above-mentioned Food Additives Code include chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid, natural additives such as persimmon extract, licorice extract, crystalline cellulose, high- A preservative formulation, a tar coloring agent, and the like.

The health functional food may be used for various foods and beverages for improving degenerative brain diseases. For example, the health functional food may be used in various foods, beverages, gums, tea, vitamin complex, health functional supplement, food additive and the like.

The health functional food may contain 1.0 to 10.0% by weight of the composition, based on the total weight, for the purpose of improving degenerative brain diseases. If the composition is less than 1.0% by weight, the effect of improving degenerative brain disease may not be sufficiently realized. If the composition is more than 10.0% by weight, the quality of the product may not be realized or the cost efficiency may be deteriorated.

The health functional food may be manufactured and processed into any one form selected from the group consisting of tablets, granules, powders, capsules, liquid solutions and rings for the purpose of improving degenerative brain diseases.

Specifically, the health functional food in the form of tablets may be prepared by granulating a mixture of a sardine extract or its fractions, an excipient, a binder, a disintegrant, and other additives in a conventional manner and then compression- Can be produced by direct compression molding. The health functional food of the tablet form may contain a mating agent and the like if necessary, and may be sieved to a suitable skin care agent if necessary.

The hard capsule of the capsule type health functional food may be prepared by filling a normal hard capsule with a mixture with an additive such as eggplant extract and excipient, or by granulating or granulating the granule or granule with the soft capsule. Fractions thereof, and excipients such as excipients into a capsule base such as gelatin. The soft capsule may contain a plasticizer such as glycerin or sorbitol, a coloring agent, a preservative and the like, if necessary.

The above-mentioned ring-type health functional food can be prepared by molding a mixture of a bovine rhubarb extract or its fractions, an excipient, a binder and a disintegrant by an appropriate method. If necessary, Talc or a suitable substance may be used.

The above-mentioned granular health functional food can be prepared into a granular form by a suitable method, and may contain a flavoring agent, a mating agent and the like if necessary, such as a sardine extract or a fraction thereof, an excipient, a binder and a disintegrant.

Further, the definitions of the above excipients, binders, disintegrants, lubricants, mating agents, flavoring agents and the like are described in documents known in the art, and the functions and the like may be the same or similar.

As described above, the bovine rhubarb extract can protect the cells from neurotoxic substances such as 6-OHDA (6-hydroxydopamine) and LPS (lipopolysaccharide) amyloid-beta to achieve a degenerative brain disease improving effect .

Specifically, the degenerative brain disease is selected from the group consisting of dementia, Alzheimer's disease, stroke, cerebral infarct, head trauma, cerebral arteriosclerosis, and Parkinson's disease. disease, and the like. However, the present invention is not limited thereto.

Another aspect of the present invention relates to a method of preparing a compound of formula Undulatai Rhizoma ) extract as an active ingredient. The action, effects and additional components of the pharmaceutical composition described above are the same as described above.

It is another aspect of the present invention are species of rhubarb (Rhei Undulatai Rhizoma ) extract as an active ingredient. The additional ingredients of the health functional food are as described above.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings, but it should be apparent that the present invention is not limited by the following embodiments.

Example  : Species  Extract preparation

After drying, the crushed seeds were extracted with 70% ethanol at room temperature for 24 hours, and then concentrated in vacuo at 40 ° C to obtain a bell pepper extract (yield: 35.8%).

Experimental Example  1: Amyloid-Beta aggregation according to extract concentration Low performance  evaluation

In order to evaluate the amyloid-β aggregation inhibition ability according to the concentration gradient of the sardine extract, HT22 cells derived from hippocampal neuronal precursor cells were seeded in a 96-well plate at 1.0 × 10 ⁵ cells / Ml and then cultured for 24 hours.

Then, the spermatogonia extract according to the above example was pretreated with 1 μg / ml, 10 μg / ml and 100 μg / ml for 1 hour, followed by further treatment with amyloid-beta at a concentration of 5 μM for 23 hours.

After each reaction, MTT (3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide) was treated at a concentration of 0.5 mg / ml for 3 hours and the absorbance was measured at 570 nm And the cell viability was expressed by the cell viability. The results are shown in Fig.

1, the cell survival rate was higher in the case of treatment with the species rhubarb extract than in the negative control (black) treated with the amyloid-beta alone, and the cell survival rate was further improved as the concentration of the species rhubarb extract was increased .

These results suggest that the sardine extracts may significantly inhibit HT22 cell death by amyloid-beta, exhibit excellent neuroprotective ability, and improve the degenerative brain disease improving effect.

Experimental Example  2: Cerebral nerve cell according to extract concentration Protection ability  evaluation

To confirm the neuroprotective ability of the sardine extract, PC12 cells derived from rat adrenal medulla chromosome-positive pheochromocytoma were dispensed into a 96-well plate at 2.5 × 10 ⁵ cells / ml And cultured for 24 hours.

Thereafter, the spermatogonia extract of the above example was pretreated at a concentration of 1 μg / ml, 10 μg / ml and 100 μg / ml for 1 hour, post-treated with 6-OHDA at a concentration of 120 μM, Lt; / RTI >

Each of the cells after completion of the reaction was treated with MTT at a concentration of 0.5 mg / ml for 3 hours, and the absorbance at 570 nm was measured and expressed as the cell viability. The results are shown in FIG.

2, the survival rate of the callus was improved in a concentration dependent manner when the callus extract was treated with a small amount of the callus extract, and the cell survival rate was improved compared to the negative control (black) treated with only 6-OHDA .

In particular, when the concentration of the sardine extract was 100 μg / ml, the cell survival rate was similar to that of the positive control, 50 μM quercetin.

These results suggest that the sardine-extracts significantly inhibit PC12 cell death by 6-OHDA, exhibit excellent neuroprotective ability and can improve the degenerative brain disease improving effect.

Experimental Example  3: Evaluation of anti-inflammatory efficacy according to extract concentration

In order to confirm the anti-inflammatory effect of the sardine extract, the hippocampus and the black pigment were cut in the brain tissue of the mouse. Astrocytes and microglia were separated from the hippocampus and black pigment, and the cells were seeded at a density of 3.0 × 10 ⁵ cells / ml on a 96-well plate and cultured for 24 hours.

Then, each of the cells was pre-treated with 10 mg / kg and 100 mg / kg of bovine rhubarb extract, cultured for 4 days, and further treated with 5 mg / kg of LPS (lipopolysaccharide) for 2 hours.

GFAP (Glial Fibrillary Acidic Protein) antibody was treated with the reacted astrocytes, the microglial cells were treated with Iba-1 antibody to stain them, and their intensities were measured. The results are shown in FIGS. 3 and 4 .

3, the extracts of rhizophora suppresses the activity of astrocytes induced by LPS in a concentration-dependent manner. In particular, the rhizome extract of 100 mg / kg shows inhibition of activity similar to that of quercetin, It can be expressed in all the astrocytes around the black pigment and hippocampus.

In addition, referring to FIG. 4, it can be confirmed that the microspheres surrounding the black pigment and the hippocampus can also inhibit the activity induced by LPS in a concentration-dependent manner by the endorphin extract.

This suggests that the extracts of the seeds can significantly inhibit the inflammatory reaction induced by LPS, a neurotoxic substance, specifically the activity of astrocytes and microglia, and furthermore, , Indicating excellent efficacy as a therapeutic composition.

It will be understood by those skilled in the art that the foregoing description of the present invention is for illustrative purposes only and that those of ordinary skill in the art can readily understand that various changes and modifications may be made without departing from the spirit or essential characteristics of the present invention. will be. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive. For example, each component described as a single entity may be distributed and implemented, and components described as being distributed may also be implemented in a combined form.

The scope of the present invention is defined by the appended claims, and all changes or modifications derived from the meaning and scope of the claims and their equivalents should be construed as being included within the scope of the present invention.

Claims (7)

A pharmaceutical composition for preventing or treating Alzheimer's disease comprising Rhei Undulatai Rhizoma extract as an active ingredient. The method according to claim 1,
The pharmaceutical composition for preventing or treating Alzheimer's disease, which is extracted with water, a C ₁ to C ₄ lower alcohol, or a mixed solvent thereof. 3. The method of claim 2,
The pharmaceutical composition for preventing or treating Alzheimer's disease wherein the lower alcohol is ethanol. delete A health functional food for preventing or ameliorating Alzheimer's disease comprising Rhei Undulatai Rhizoma extract as an active ingredient. delete delete

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