KR20180109297A - Composition for antiinflammatory and inflammatory neurodegenerative diseases comprising rubus coreanus extract - Google Patents

Abstract

The present invention relates to a composition for antiinflammatory and inflammatory neurodegenerative diseases comprising an extract of Rubus coreanus byproducts.

Description

Technical Field [0001] The present invention relates to a composition for preventing or treating inflammatory and inflammatory neurodegenerative diseases, which comprises a bacterium by-product extract, a composition for preventing or treating inflammatory and inflammatory neurodegenerative diseases,

The present invention relates to a composition for preventing or treating anti-inflammatory and inflammatory neurodegenerative diseases, which comprises a bacterium by-product extract.

Rubus coreanus Miquel fruits) is a perennial deciduous broad-leaved shrub belonging to the Rosaceae and originates in Korea, China, and Japan. The bokbunja blooms in May to June with light pink flowers, and the fruit is harvested from July to August. Bokbunja contains minerals such as iron, potassium, phosphorus, ascorbic acid and various kinds of organic acids. It contains phenolic compounds such as quercetin and kamferol, and hydrolyzable tannins. In addition, the natural water-soluble anthocyanin pigment known as a functional substance is contained, and it is started to be cultivated by the ingestion of raw materials, sales of various processed products such as drinks, beverages and vinegar. In this study, we investigated the effects of 4-hydroxybenzoic acid, 3,4-hydroxy-3-methoxybenzoic acid quercetin, 4-dihydroxybenzoic acid and various phenolic acids and cyanidin-3-O-rutinoside ), cyanidin-3-O-glucoside (C3G), and cyanidin-3-rhamnoglucoside, and hydrolyzable tannins gallic acid, 2-3 (S) -HHDP-D-glucopyranose and sanguin H -4 and H-6. Ellagitinin, flavan-3-ol, proanthocyanidin on the stem, kaemp-ferol, quercetin, quercetin 3-O-β-D-glucuronide (Q3G) sodium salt, Q3G sodium carboxylate and ellagitannin ellagic acid, sanguinin H-5, etc., and it is reported that bokbunja seed contains a fatty acid such as phytosterin. According to the report on the efficacy of bokbunja so far, it is known that the herbaceous bokbunja and dried ones are used as herbal medicines, and liver function enhancement, thirst relief, sexual function enhancement, vision protection, improvement of urination and increase of energy are known. In addition, it has been reported that it has antitumor and cancer-inducing activity, anti-inflammatory effect, diabetic effect, cholesterol-lowering action, and dressing action. Bokbunjae has the highest antioxidant activity among fruits and vegetables, has bone protective effect, and has antibacterial and antiviral activity against pathogenic bacteria. It started to plant bokbunja since 1997 and shipped bokbunja in full production since 1999 and shipped bokbunja, beverage, etc., and the by-product was composted and discarded. However, the area of cultivation is increased and the amount of byproduct is increased. .

On the other hand, there are antioxidant enzymes that protect against reactive oxygen species in the body such as superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), glutathione reductase and glutathione-S- transferase. However, The role of antioxidant system in the human body due to substances, smoking, stress, etc., exceeds the defense system and causes protein degradation and DNA damage.

Therefore, synthetic materials such as butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) have been developed as antioxidants. However, studies on finding dietary antioxidants that are safe from nature have been actively carried out .

Inflammation, on the other hand, is a defense mechanism to prevent damage to human tissues caused by infection, which involves symptoms such as development, fever and pain. If the inflammatory reaction is repeated for a long period of time, it can cause various chronic diseases such as neurodegenerative diseases and cancer.

Macrophages are involved in and regulate the production of inflammatory mediators such as nitric oxide (NO), prostaglandin (PG) and pro-inflammatory cytokines in the human immune response. These inflammatory mediators induce an inflammatory response and, if the host immune response does not respond appropriately, induce inflammatory diseases.

Korean Patent Laid-Open Publication No. 1020120011981 discloses a dermal extract having anti-inflammatory effect and a composition for external application for skin comprising the same, wherein the dermal extract increases the expression of hemeoxygenase-1 and sirtuin-1 It has an anti-inflammatory effect.

The present invention has been made in view of the above needs, and an object of the present invention is to provide an anti-inflammatory composition.

It is another object of the present invention to provide a composition for treating or preventing inflammatory neurodegenerative diseases.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating inflammatory neurodegenerative diseases, comprising an extract of bokbunja by-products as an active ingredient.

In one embodiment of the invention, the composition is preferably but not limited to weaken inductive nitrogen oxide synthesis (iNOS) and NO production.

In another embodiment of the present invention, the extract is preferably a bokromatic by-product alcohol extract, more preferably an ethanol extract, but not limited thereto.

In another embodiment of the present invention, the composition preferably inhibits microglial cell activity in microglial cells, but is not limited thereto.

In addition, the present invention provides a food composition for relieving inflammatory neurodegenerative diseases, which comprises an extract of bokromatic by-products as an active ingredient.

The present invention also provides a pharmaceutical composition for antiinflammation comprising an extract of bokbunja by-product as an active ingredient.

The present invention also provides a functional food composition for anti-inflammation comprising an extract of bokbunja by-product as an active ingredient.

The present invention also provides a composition for antioxidation comprising an extract of bokromatic by-products as an active ingredient.

The pharmaceutical composition comprising the bacterium by-product extract of the present invention as an active ingredient may be prepared by using pharmaceutically acceptable and physiologically acceptable adjuvants in addition to the above-mentioned effective ingredients. Examples of the adjuvants include excipients, disintegrants, sweeteners, A binder, a coating agent, a swelling agent, a lubricant, a lubricant or a flavoring agent.

The pharmaceutical composition may be formulated into a pharmaceutical composition containing at least one pharmaceutically acceptable carrier in addition to the above-described active ingredients for administration.

The pharmaceutical composition may be in the form of granules, powders, tablets, coated tablets, capsules, suppositories, liquids, syrups, juices, suspensions, emulsions, drops or injectable solutions. For example, for formulation into tablets or capsules, the active ingredient may be combined with an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. Also, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included as a mixture. Suitable binders include, but are not limited to, natural sugars such as starch, gelatin, glucose or beta-lactose, natural and synthetic gums such as corn sweeteners, acacia, tracker candles or sodium oleate, sodium stearate, magnesium stearate, sodium Benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum and the like. Acceptable pharmaceutical carriers for compositions that are formulated into a liquid solution include sterile solutions suitable for the living body such as saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, One or more of these components may be mixed and used. If necessary, other conventional additives such as an antioxidant, a buffer, and a bacteriostatic agent may be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate into injectable solutions, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like. Further, it can be suitably formulated according to each disease or ingredient, using the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA as an appropriate method in the field.

The present invention also provides a food composition comprising the brambled by-product extract.

The food composition according to the present invention can be formulated in the same manner as the above 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, meats, chocolates, foods, confectionery, pizza, ramen noodles, gums, ice cream, alcoholic beverages, vitamin complexes, .

The present invention provides a health functional food comprising the composition.

The present invention also provides the use of the composition comprising the bacterium by-product extract as an active ingredient for the manufacture of medicines or foods for the prevention and treatment of tuberculosis. The composition of the present invention comprising the bacterium by-product extract as an active ingredient can be used for the preparation of medicines or foods for the prevention or treatment of diseases related to the prevention and treatment of tuberculosis.

The present invention also provides a method of preventing or treating an inflammatory disease comprising administering to a mammal a therapeutically effective amount of a bursal by-product extract.

The term "mammal " as used herein refers to a mammal that is the subject of treatment, observation or experimentation, preferably a human.

As used herein, the term "therapeutically effective amount " refers to the amount of active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal or human, as contemplated by a researcher, veterinarian, This includes an amount that induces relief of the symptoms of the disease or disorder being treated. It will be apparent to those skilled in the art that the therapeutically effective dose and the number of administrations of the active ingredient of the present invention will vary depending on the desired effect. Thus, the optimal dosage to be administered can be readily determined by those skilled in the art and will vary with the nature of the disease, the severity of the disease, the amount of active and other ingredients contained in the composition, the type of formulation, and the age, The age, body weight, sex, diet, time of administration, route of administration and fraction of the composition, duration of treatment, concurrent medication, and the like.

The dose of the bacterium by-product extract as an active ingredient in the pharmaceutical composition of the present invention can be 6 to 30 times per kg of body weight once or three times a day depending on the patient's age, sex, symptom, method of administration, or prevention purpose have. Dosage levels for patients exhibiting the specific symptoms may vary depending on the patient's body weight, age, sex, health condition, diet, time of administration, administration method, excretion rate, severity of disease, and the like.

In the therapeutic method of the present invention, the composition comprising the bacterium by-product extract of the present invention as an active ingredient can be administered orally, rectally, intravenously, intraarterially, intraperitoneally, intramuscularly, intrasternally, transdermally, topically, And can be administered in a conventional manner.

The composition comprising the bacterium by-product extract according to the present invention as an active ingredient provides antioxidative and anti-inflammatory effects through excellent radical scavenging ability, inhibition of nitrogen monoxide (NO) formation, and the like.

FIG. 1 is a graph showing the DPPH inhibition effect of the bokbule by-product extract. FIG.
FIG. 2 is a graph showing cell viability (BV-2 cells) of bokbule by-product extract. FIG.
FIG. 3 is a graph showing inhibition of NO production of bokbunja by-product extract. FIG.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these examples are for illustrative purposes only and that the scope of the present invention is not construed as being limited by these examples.

Example  1: Bokbunja by-product extraction

Bokbunja byproduct was purchased from Gochang, Jeonbuk Province and 100 g of bokbunja byproduct was extracted with 1 L of ethanol for 72 hours at room temperature.

Example  2: Antioxidant

The DPPH radical scavenging activity of the bacterium by-product extract was determined by adding 30 μL of the extract solution and 30 μL of the 60 μM DPPH solution dissolved in ethanol to the capillary tube for 2 minutes at room temperature. The electron spin resonance (ESR) spectrometer -PX 2300, JEOL, Japan). At this time, the measurement conditions of the ESR spectrophotometer were 336.5 ± 5 mT for the magnetic field, 5 mW for the microwave power, 9.41 GHz for the modulation frequency, and the DPPH free radical scavenging activity (% As a result, the DPPH was measured to determine the antioxidant capacity of the bacterium by-product extract (RCB). DPPH radicals were measured using an ESR instrument. Each sample is shown to be excellent in antioxidant effects because it reduces the signal in a concentration dependent manner.

Example  3: cell survival rate

In order to examine the effect of LPS and bacterium by-product extract on cell viability in BV-2 cells stimulated with LPS, cell biability was measured using 3- [4,5-Dimethylthiazol-2-yl] -2,5-diphenyl-tetrazolium bromide MTT) assay.

Cells (1 × 10 ⁵ cells / ml) were seeded in a 96-well plate (180 μL), cultured in a CO2 incubator for more than 12 hours, and cultured for 24 hours. After culturing, the culture medium was removed, and 200 μL of the medium containing 0.5 mg / mL MTT was added, followed by incubation for 4 hours to reduce the MTT. After removing the culture medium, 100 μL of dimethylsulfoxide (DMSO) was added and the resulting formazone crystals were dissolved. The absorbance was measured at 540 nm using an ELISA reader. Cell viability was expressed as percentage (%) as compared with control.

As a result of cell viability measurement, it was confirmed that cell survival rate was not changed in all the experimental groups treated with LPS and bacterium by-product extract alone or together (FIG. 2).

This indicates that the inflammation inducing substance, LPS and bokbunja by-product extract do not affect cell survival.

Example  4: By LPS  Concentration-dependent NO production inhibition of brucule by-product extract in activated glial cells

In order to analyze the anti - inflammatory effect of Bokbunja by - product extract, we investigated whether LPS, an inflammation inducer, has an effect on the concentration of NO produced in stimulated glial cells.

NO was determined by seeding 5 × 10 ⁵ cells / well in a 24-well plate, adding LPS and extracts at different concentrations, reacting in a 24 h incubator, and then adding 50 μL each of Griess reagent (1% sulfanilamide / After reacting with 0.1% N- (1-naphthyl) -ethylenediamine dihydrochloride / 2.5% H3PO4), the value is measured using a Sunrise basic 96-well microplate spectrophotometer (TECAN AUSTRIA) with a wavelength of 540 nm.

NO was induced by LPS (100 ng / mL) in the glial cells, which was about 20 μM, which was about 10 times higher than that of 2 μM used as a control. In the experimental group, , 500, and 1,000 ㎍ / mL, respectively, indicating that the NO production was reduced in a concentration dependent manner by the brucule by-product extract (Fig. 3).

Claims (11)

A pharmaceutical composition for the prevention or treatment of inflammatory neurodegenerative diseases, comprising a bacterium by-product extract as an active ingredient. The pharmaceutical composition for preventing or treating inflammatory neurodegenerative diseases according to claim 1, wherein the composition weakens inducible nitric oxide synthase (iNOS) and NO production. The pharmaceutical composition for preventing or treating inflammatory neurodegenerative diseases according to claim 1, wherein the extract is an alcohol extract of bokromatic by-products. The pharmaceutical composition for preventing or treating inflammatory neurodegenerative diseases according to claim 1, wherein the composition inhibits microglial cell activity in microglial cells. A food composition for relieving inflammatory neurodegenerative diseases, comprising a bacterium by-product extract as an active ingredient. 6. The food composition according to claim 5, wherein the food is beverage, jelly, candy, gum or dairy product. A pharmaceutical composition for antiinflammation comprising bokbunja by-product extract as an active ingredient. [Claim 7] The pharmaceutical composition according to claim 7, wherein the extract is bokromatic by-product extract. 8. The pharmaceutical composition according to claim 7, wherein the composition weakens inductive NOx NO production. A functional food composition for antiinflammatory activity comprising bokbunja by-product extract as an active ingredient. An antioxidative composition comprising bokbunja by-product extract as an active ingredient.

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