KR20160082029A - Composition for curing asthma containing extract of salvia plebeia leaft and extract of fermented allium hookeri root - Google Patents

Abstract

The present invention relates to a composition for treating asthma, comprising an extract of Salvia plebeian leaves and an extract of fermented Allium hookeri roots and, more specifically, relates to a pharmaceutical composition for preventing or treating asthma, comprising an ethanol extract of Salvia plebeian leaves and an extract of fermented Allium hookeri roots as an active ingredient, and to a food composition for alleviating asthma. When mixing the ethanol extract of Salvia plebeian leaves and the extract of fermented Allium hookeri roots and using the same, the production of nitrogen monoxide, and IL-6, IL-4, TNF-α, and IFN-γ, which are asthma-related factors can be inhibited in an effective manner, thereby having effects in treating asthma.

Description

FIELD OF THE INVENTION [0001] The present invention relates to a composition for treating asthma, which comprises an extract of Leuconostoc sp. Leaf extract and a fermented trifoliate root.

The present invention relates to a composition for treating asthma, which comprises an extract of Leucospora japonica leaf and an extract of fermented Trichomoniasis root, and more particularly to a composition for treating asthma comprising an ethanol extract of Leucospora japonica leaf and an ethanol extract of fermented trifoliate roots as an active ingredient A pharmaceutical composition for the prevention or treatment of asthma and an improved food composition.

Salvia plebeia is a biennial plant of the family Lamiaceae. It is said to have a shape like a pale green leaf, and it is called a serpentine cabbage. Also, it is also called "Nogincho", "Nogincho", "Watery ears", and "Pongchungjeong". It is also called "枝 草" because it is a grass with fragrant branches. Leaves are 3 ~ 8cm in length and come together on the roots and spread on the ground, facing each other, with dull serrations on the edges of the leaves, occasionally small hairs on the front and back, and long petiole. When it is young, it is squashed and flat on the ground, it is wintered, and as it grows, its leaves are squashed, gently curved, and grow up straight.

Allium hookeri are distributed in southern China, India, Bhutan, Sri Lanka, etc. in East Asia and grow in forests, wetlands and grasslands of 1400m to 4200m above sea level. It is also called "Root Leek". It is also called "玄 菜" because its taste and shape are similar to ginseng. It is also called "三 菜" because it has three flavors of bitter taste, sweet taste and spicy taste. The height of the plant is about 0.6 to 1 m, and it is known that the roots, leaves and flowers of the three-leafed plants can be used for food and medicinal use. In the past three years, the area of cultivated triplicate cultivated land has increased 30 times in Korea, and the number of cultivated farmhouses has increased more than 90 times in Korea.

The incidence of asthma varies according to country, race, and age. However, according to the report of the United Kingdom in 1991, it is reported that about 7% of adults and 13.5% of children are of age group. In Korea, The trend is gradually increasing. Currently developed and used bronchodilators and steroid drugs can not be cured, and many side effects may accompany long-term use. Therefore, there are active researches on therapeutic drugs using natural products with no risk and low physiological side effects.

However, natural extracts do not have side effects, but they have weaknesses. Therefore, it is necessary to study the combination of natural substances that have synergistic effects in treating asthma. Korean Patent No. 10-1045025 and Korean Patent Publication No. 2010-0094015 disclose patents relating to a composition for treating asthma by a combination of various natural substances.

1. Korean Patent No. 10-1045025 2. Korean Patent Publication No. 2010-0094015

Accordingly, the inventors of the present invention have found that the effect of treating asthma is significantly enhanced by using ethanol extract of Leucosporium japonica leaf and ethanol extract of fermented Trichomoniasis root, and completed the present invention.

Accordingly, an object of the present invention is to provide a pharmaceutical composition for preventing or treating asthma containing ethanol extract of Salvia plebeia leaf and ethanol extract of fermented Allium hookeri root as an active ingredient.

Another object of the present invention is to provide a method of treating Salvia plebeia ) ethanol extract and fermented trifoliate ( Allium hookeri ) roots as an active ingredient. The present invention also provides a food composition for preventing or ameliorating asthma.

In order to achieve the object of the present invention, the present invention provides a pharmaceutical composition for preventing or treating asthma comprising ethanol extract of Salvia plebeia leaf and ethanol extract of fermented Allium hookeri root as an active ingredient .

In order to achieve another object of the present invention, the present invention relates to an ethanol extract of Salvia plebeia leaf and an Allium hookeri ) roots as an active ingredient. The present invention also provides a food composition for preventing or ameliorating asthma.

When ethanol extracts of P. japonicus leaf and ethanol extracts of fermented trifoliate were used, IL-4, IL-6, IFN-γ and TNF-α and monoclonal The generation of nitrogen can be remarkably suppressed, and asthma can be effectively treated.

FIG. 1 (A) shows the NO production inhibitory effect of the leaf ethanol extract and the root ethanol extract of P. japonicus.
FIG. 1B shows the inhibitory effect of leaf ethanol extract and root ethanol extract of Laureus chase on IL-6 production.
Fig. 2 (A) shows the NO production inhibitory effect of the fermented trifoliate root extract.
Fig. 2B shows the inhibitory effect of fermented trifoliate root extract on IL-6 production.
FIG. 3 shows the NO production (%) of ethanol extract of Leuconchocyzate leaves, ethanol extract of fermented trifoliate roots, and the mixture of the two substances.
Fig. 4 shows the amount (%) of IL-6 production of the ethanol extract of Leucocephala japonica leaf, the ethanolic extract of fermented trifoliate root, and the mixture of the two substances.
FIG. 5 shows the amount of IFN-y production (%) of the ethanol extract of Leucocephala leaf, the ethanol extract of fermented trifoliate root, and the mixture of the two substances.
FIG. 6 shows the amount of TNF-α produced in the mixture of the ethanol extract of Leucoceans tea, the ethanol extract of the fermented trifoliate root, and the two substances.
Fig. 7 shows the amount of IL-4 production (%) of the ethanol extract of Leuconostoc sp. Leaves, the ethanol extract of fermented trifoliates root, and the mixture of the two substances.

The present invention provides a pharmaceutical composition for preventing or treating asthma comprising ethanol extract of Salvia plebeia leaf and ethanol extract of fermented Allium hookeri root as an active ingredient.

The fermented trifoliate root in the extract of the fermented trifoliate root can be produced by fermentation with Saccharomyses cerevisiae . The fermentation method is not limited thereto, but can be fermented at 40 to 50 ^° C for 7 to 10 days.

The pharmaceutical composition of the present invention may be effective for the treatment of acute asthma, although it is not limited thereto.

It has been reported that IL-6 (interleukin-6) is produced from macrophages in patients with acute asthma, and IL-6 gene and protein expression is also increased in asthmatic bronchial epithelial cells [Gosset PA. et al ., J Allergy Clin Immunol; 153: 561-71, 1991, & Bradding PJ. et . al . , Am J Respir Cell Mol Biol; 10-471-80, 1994]. IL-6 is significantly increased in patients with acute asthma than in patients with asymptomatic asthma. IL-6 plays an important role in various immunological and inflammatory effects initiated by infection or tissue damage. IL-6 is involved in the stimulation of B cell differentiation and antibody secretion, activates T cells and natural killer cells, Lt; / RTI > Am J Respir Crit Care Med , 151; 1354-8, 1995, reported that serum IL-6 levels were increased in patients with asymptomatic asthma compared with normal controls. Serum levels were significantly increased in acute asthmatic patients than in asymptomatic patients, In patients with asthma, serum IL-6 levels are associated with aggravation of asthma symptoms and pathophysiology.

In addition, secretion inhibition of IL-4 and TNF-α is known to suppress allergic and inflammation-related cytokine secretion in immune cells. Thus, inhibition of the production of IL-4, IL-6, and TNF- [alpha] is an important mechanism in the treatment of asthma, particularly acute asthma.

Nitric oxide (NO) is known to be a factor associated with bronchitis in asthma. Asthma is an inflammatory disease of the airways and can be diagnosed by examining eosinophil inflammation. Nitric oxide (NO) is produced in mast cells, epithelial cells, endothelial cells and macrophages of the lungs and airways, [Asthma and allergy, Vol. 32, No. 2, Jun, 2012]. Since NO production is increased in cells of asthmatic patients than in normal human cells, whether or not NO production is reduced can be used to determine whether asthma improvement is effective. The level of IFN-γ is closely related to the severity of asthma, airway hyperresponsiveness, and eosinophilia in the blood [Magnan et al., Am J Respir Crit Care and Med., Vol.161, No.6, A significant increase in IFN-γ levels was reported in clinical trials in patients with asthma [Choi, Jun-Yong et al., 7 (1), 10g / ml ) Decreased the expression of IFN-γ by 23.3% and 17.6%, respectively [Jong Hoon Yoo, et al., Korean Journal of Oriental Medicine 30, Volume 3, 2009].

In view of the above, it is considered that a substance that inhibits the production of IL-4, IL-6, TNF-α, IFN-γ and NO can treat or ameliorate asthma. The asthma may in particular be acute asthma.

The pharmaceutical composition according to the present invention may contain an ethanol extract of Laureus chafer leaf and an ethanol extract of a fermented trifoliate root as an active ingredient, and may include a pharmaceutically acceptable carrier, excipient or diluent. Dosage forms of the compositions of the present invention may be used in the form of their pharmaceutically acceptable salts and may also be used alone or in combination with other therapeutically active compounds as well as in suitable combinations. The salt is not particularly limited as long as it is pharmaceutically acceptable so long as it is pharmaceutically acceptable and includes, for example, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrofluoric acid, hydrobromic acid, formic acid acetic acid, tartaric acid, lactic acid, citric acid, fumaric acid, Sulfonic acid, benzenesulfonic acid, toluenesulfonic acid, and naphthalenesulfonic acid.

The compositions of the present invention may be of various oral or parenteral formulations. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may contain one or more excipients such as starch, calcium carbonate, sucrose or lactose lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like.

The preferred dosage of the pharmaceutical composition according to the present invention varies depending on the condition and the weight of the patient, the degree of the disease, the drug form, the administration route and the period, but can be appropriately selected by those skilled in the art. However, for the desired effect, the pharmaceutical composition of the present invention may be administered in an amount of 0.001 to 100 mg / kg divided once to several times a day.

Dosage forms of the pharmaceutical compositions according to the present invention may be used in the form of their pharmaceutically acceptable salts and may also be used alone or in combination with other pharmaceutically active compounds as well as in suitable aggregates.

The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, livestock, and humans in various routes. All modes of administration may be expected, for example, by oral, intraperitoneal, rectal or intravenous, intramuscular, subcutaneous, intrathecal or intracerebral injection.

The present invention relates to the use of Salvia The present invention provides a food composition for preventing or ameliorating asthma comprising an ethanol extract of a plebeia leaf and an ethanol extract of a fermented trifoliate root as an active ingredient.

The food composition according to the present invention can be used alone or in combination with other food or other food ingredients, and can be suitably used according to a conventional method, with the ethanol extract of Laureus chafer leaf and the ethanol extract of fermented trifoliate root.

The food composition according to the present invention includes components that are ordinarily added during the manufacture of food products, and includes, for example, proteins, carbohydrates, fats, nutrients, and seasonings.

There is no particular limitation on the kind of the food. Examples include dairy products including meats, sausages, breads, chocolates, candies, snacks, confections, pizza, ramen noodles, other noodles, gums and ice cream, soups, drinks, tea, drinks, alcoholic beverages, , And health foods in a conventional sense.

The food composition according to the present invention may contain various flavors or natural carbohydrates as additional components such as ordinary beverages. Such natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like. The ratio of the natural carbohydrate may be generally about 0.01 to 0.04 g per 100 ml of the composition of the present invention.

Furthermore, the food composition according to the present invention can be used as a nutritional supplement, a vitamin, an electrolyte, a flavoring agent, a coloring agent, a pectic acid and its salt, an alginic acid and its salt, an organic acid, a protective colloid thickening agent, a pH adjusting agent, a stabilizer, , A carbonating agent used in carbonated drinks, and the like. In addition, the food composition of the present invention may contain flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not critical, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the food composition of the present invention.

The mixed weight ratio of the ethanol extract of Leucoschis caballus leaf and the extract of the fermented Trichotomillus root contained in the pharmaceutical composition and the food composition of the present invention may be 6: 4 to 8: 2, though not limited thereto. In the above range, the amount of cytokines such as IL-6, IFN-y, TNF-a, and IL-4 is rapidly decreased, and thus the effect of treating asthma is remarkably high.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood that the scope of the present invention is not limited by these examples in accordance with the gist of the present invention, and it is to be understood by those skilled in the art that the present invention is not limited thereto It will be obvious.

< EXAMPLES Preparation of extract  >

The roots and leaf parts of Salvia plebeia were separately washed and lyophilized. The lyophilized leaves and roots were pulverized using a grinder. Each powder was added 40 times (w / v) of 70% ethanol for 48 hours, followed by concentration and lyophilization to obtain an ethanol extract.

The fermented triple root extract was prepared by washing the roots of Allium hookeri and then cultivating Saccharomyses cerevisiae MG111 (Mediogen, Korea), previously cultured, at a concentration of 1 × 10 ⁹ cfu / g And fermented for 9 days at 40-50 ^° C. Thereafter, an ethanol extract was prepared in the same manner as in the above-described method for producing an ethanol extract of Baeam japonica.

In order to investigate the synergistic effect of Leaf Chaetzia ficus-indica Leaf Extract and Fermented Leaf Leaf Extract, the extracts of Baccaraceae and Fermented Tripeaceae were mixed at a weight ratio of 1: 9, 3: 7, 5: 5, 7: Each sample was prepared by mixing.

< Experimental Example Comparison of asthma treatment effect >

The macrophage cell line RAW 264.7 (KCLB 40071) was dispensed into each well of a 24-well plate at a density of 3 × 10 ⁶ cells / LPS, and then treated with LPS (Lipopolysaccharides) at a concentration of 4 μg / Three kinds of samples prepared in the examples (Leaf tea leaf extract, fermented trifoliate root extract and mixture thereof) were treated at a concentration of 200 μg / ml and cultured at 37 ° C. for 24 hours. Controls did not process any material.

(IL-6), IL-4, TNF-α, and IFN-γ levels were measured after culturing.

The amount of NO was determined by adding 100 ㎕ of 50 ㎕ supernatant and Griess reagent (TB229, Promega, USA), and then measuring the absorbance at 520 ~ 550 nm. The concentration of nitrite produced was calculated from the nitrite standard curve.

IL-6 (ab100712, abcam, UK), IL-4 (M4000B, R & D systems, USA), TNF-α (SMTA00B, R & D systems, USA) and IFN- Analysis was carried out using an assay kit. 100 μl of the supernatant was dispensed into a microplate on which a primary antibody was immobilized, and immobilized for 2 hours. After washing 5 times with washing solution, biotinylated antibody was applied and reacted for 2.5 hours. After washing, 100 μl of streptavidin solution was added to the plate for reaction for 45 minutes. After washing, TBM substrate was treated, and the absorbance was measured at 450 nm for 30 minutes. The concentration of each cytokine (IL-6, IL-4, TNF-α, IFN-γ) produced was calculated from the standard curve for each cytokine. The results of the control group were set at 100%, and the results of the other experimental groups were expressed as a percentage relative to the control group results.

The results of the experimental group treated with the leaf ethanol extract and the root ethanol extract of Laccase japonica were shown in Fig. 1, and the results of the experimental group treated with the fermented trifoliate ethanol extract were shown in Fig. All results were repeated three times or more, and the data were expressed as mean standard error (meanSE). Statistical analysis was performed using the SPSS program (version 12.0 Apache Software, SPSS Inc.) and Duncan's multi-range test was used to verify significant differences ( p < 0.05) between the samples.

In the case of NO production in FIG. 1, it was found that the amount of NO produced in the experimental group treated with the mulberry extract was significantly lower than that of the control, and that there was no significant difference between the extracts of the mulberry leaf and the root. As for the amount of IL-6 production, root extract of Chamaecyparis obtusa showed a more significant difference than control of leaf extract.

In addition, in FIG. 2, the NO production amount of the fermented trifoliate root extract was not significantly different from the control group, and the amount of IL-6 production was significantly lower.

To investigate the synergistic effect of leaf extract and fermented trifoliate root extract of Baeam Cha chi, the mixture of the two substances prepared in the above examples mixed at various weight ratios was used as a sample and NO and four cytokines (IL- 6, IL-4, TNF-α, and IFN-γ. The same test was conducted as in the above-mentioned experiment in which the above substances were treated alone, and the statistical significance test was also used. As a result, when two substances were mixed with each other than the case of using alone, the effect was remarkably superior to the predicted result. Especially, when the leaf extract of Baeam Cha and the ethanol extract of the fermented trifoliate root were mixed at a weight ratio of 7: 3, the synergistic effect was excellent. From the above results, it can be seen that the leaf extract of Baeam Cha Cha and the fermented trifoliate root extract are synergistic substances in the treatment of asthma, and the synergistic effect is remarkably high at a specific ratio (6: 4 to 8: 2).

Claims (7)

A pharmaceutical composition for preventing or treating asthma comprising ethanol extract of Salvia plebeia leaf and ethanol extract of fermented Allium hookeri root as an active ingredient.
The method according to claim 1,
The above-mentioned fermented tuberous roots were used as the saccharomyces roots in Saccharomyses cerevisiae . &lt; / RTI &gt;
The method according to claim 1,
Wherein the asthma is acute asthma.
The method according to claim 1,
Wherein the ethanol extract of the Baeam japonica leaf and the ethanol extract of the fermented trifoliate root are mixed at a weight ratio of 6: 4 to 8: 2.
Salvia The present invention relates to a food composition for preventing or ameliorating asthma, which comprises an ethanol extract of a plebeia leaf and an ethanol extract of a fermented allium hookeri root.
6. The method of claim 5,
Wherein the fermented tuberous root is fermented with Saccharomyses cerevisiae .
6. The method of claim 5,
Wherein the ethanol extract of the Baeam japonica leaf and the ethanol extract of the fermented trifoliate root are mixed at a weight ratio of 6: 4 to 8: 2.

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