KR100555653B1 - Composition comprising an extract of processed Panax genus plant for preventing and treating anxiety - Google Patents

Abstract

The present invention relates to a composition for the prevention and treatment of anxiety, containing a processed extract of Panax genus plants with enhanced efficacy, ginsenoside (Rg3 + Rg5 + Rk1) / (Rb1 + Rb2) The ginseng extract obtained by special processing so that the ratio of + Rc + Rd) is 1.0 or more is excellent in anti-anxiety effect, and can be used as a pharmaceutical and health functional food useful for the prevention and treatment of anxiety symptoms.

Panax genus, ginseng, anti-anxiety, extracts, compositions, pharmaceuticals, dietary supplements.

Description

Composition comprising an extract of processed Panax genus plant for preventing and treating anxiety}             

1 is a comparison of the anti-anxiety effect of white ginseng and special processed ginseng, showing the number of times the open cancer entered,

Figure 2 is a comparison of the anti-anxiety effect of white ginseng and special processed ginseng, showing the time spent in open cancer,

Figure 3 is a diagram showing the number of times entered into the open cancer to compare the efficacy of the fraction of special processed ginseng,

Figure 4 is a diagram showing the time spent in open cancer to compare the efficacy of each fraction of special processed ginseng.

The present invention relates to an anti-anxiety agent containing a processed extract of the genus Panax plant with enhanced efficacy.

Many people experience emotional stress or anxiety, but the duration is short and light, so medication is unnecessary, but sometimes anxiety can interfere with work. In addition, symptoms of anxiety may cause symptoms of mental illness. People with anxiety are more likely to have panic, worry, tension, startle, and phobia than normal people. Sedatives are medicines that alleviate the symptoms of anxiety. In particular, benzodiazepines are the most used anti-anxiety agents (anxiolytic), such as buspirone (serotonin agonist) is known. However, these drugs are used to treat anxiety, so they are not suitable for those who have mild anxiety such as nervousness, sportsmen who lack confidence, and businessmen who suffer from excessive stress. Therefore, it is very important to develop materials that can overcome anxiety without side effects.

Ginseng is a perennial plant belonging to the genus Panax, and the genus Panax is a perennial root of the genus Araliaceae. Representative species include Panax ginseng , Panax quinquefolia , Panax ginseng , Panax notoginseng , Panax japonica , Panax trifolia , Panax pseudoginseng , and Panax vietnamensis. (Understanding Korea Ginseng, p. 9, Korea Ginseng Society, 1995; Advances in Ginseng Research, pp. 127-137, Korea Ginseng Society, 1998). Other Panax genus plants include Panax elegans Gatti climb (Panax elegatior), Panax Wan Jia Taunus (Panax wangianus), Panax non pinra typhus (Panax bipinratifidus).

The most important component in these Panax plants is saponin. In particular, the Panax genus contains a common saponin in which 1-4 sugars are bound to a dammarane skeleton unlike other plants. In particular, saponins with high content in Korean ginseng are ginsenosides Rb1, Rb2, Rc, Rd, Rg1 and Re. These saponin components show various effects, and the types and strengths of the drugs vary greatly depending on their structure (Understanding Goryeo Ginseng, Korea Ginseng Society, 1995).

Ginseng has long been known to be effective for fatigue recovery and strength enhancement. In fact, ginseng is known to have increased exploratory activity, decreased spontaneous exercise, increased seizure threshold, increased memory, and analgesic effects (Understanding Korean Ginseng, Korea Ginseng Society, 1995). In addition to these effects, it has been applied to improvement of anxiety neurosis, insomnia, depression, and postpartum psychiatric symptoms (herbal medicine, Hakchangsa, 2003).

However, the ginseng's effect is very weak. Recently, there have been attempts to enhance the efficacy of ginseng by applying various processing methods to ginseng. The most representative method is the method developed by Park et al. Park et al. Developed a method of specially processing ginseng under high temperature and high pressure conditions (Korean Patent No. 192678, US Patent No. 5776460). In this process, ginsenosides Rb1, Rb2, Rc, and Rd, which are mainly contained in ginseng, are changed to ginsenosides Rg3, Rg5, and Rk1, which are not present in ginseng, and various new medicinal ingredients are produced to prevent antioxidant , Anticancer activity, and blood circulation improvement are greatly enhanced (Kim et al., Journal of Natural Products, Vol. 63, pp. 1702-1704, 2000; Vol. Et al., Journal of Chromatography A, vol. 921, pp. 335-339, 2001 year). In particular, the potency of Rg3, Rg5, Rk1 is known to be strong, but the anti-anxiety effect of these ingredients and specially processed ginseng has not been studied.

The present inventors processed ginseng specially processed ginseng so that the sum of the content of ginsenosides Rg3, Rg5, Rk1 is higher than the sum of the content of ginsenosides Rb1, Rb2, Rc, Rd is superior to conventional white ginseng. It was confirmed that there is an anti-anxiety effect, in particular, the fraction containing Rg3, Rg5, Rk1 was found to have a strong effect to complete the present invention.

Therefore, an object of the present invention is to process the Panax genus plants by specially processing the Panax genus plants to increase the active ingredient so that the ratio of ginsenosides (Rg3 + Rg5 + Rk1) / (Rb1 + Rb2 + Rc + Rd) is 1.0 or more It is to provide the use of the extracts and fractions as anti-anxiety, anti-stress, anti-depressant.

In order to achieve the above object, the present invention contains an extract of the processed Panax genus plants in which the active ingredient is increased so that the ratio of ginsenosides (Rg3 + Rg5 + Rk1) / (Rb1 + Rb2 + Rc + Rd) is 1.0 or more. It provides a composition for preventing and treating anxiety symptoms.

Provided that Rg3 includes two isomers (20-S) and (20-R).

The processed Panax genus plants may be prepared by heat treatment at a high temperature of 120 to 180 ℃ for 0.5 to 20 hours.

In addition, the genus Panax ginseng ( Panax ginseng ), American ginseng ( Panax quinquefolia ), ginseng (samchil, Panax notoginseng ), bamboo shoots ( Panax japonica ), trifolium ( Panax trifolia ), Himalayan ginseng ( Panax pseudoginseng ), Plants such as outposts, roots, stems, or leaves of Panax vietnamensis , Panax elegatior , Panax wangianus , or Panax bipinratifidus do.

The extract refers to an extract soluble in water, lower alcohols of C1 to C4 and mixed solvents thereof, preferably 70% ethanol or butanol.

In addition, the present invention is anxiety containing a non-solvent solvent soluble extract of the processed Panax genus plants with increased active ingredient so that the ratio of ginsenosides (Rg3 + Rg5 + Rk1) / (Rb1 + Rb2 + Rc + Rd) is 1.0 or more Provided are compositions for the prevention and treatment of symptoms.

The non-polar solvent soluble extract means a non-polar solvent such as hexane, chloroform, methylene chloride, ether, ethyl acetate, more preferably an extract soluble in ether.

The present invention also provides an anti-anxiety agent containing at least one component selected from ginsenosides (20S) Rg3, (20R) Rg3, Rg5, and Rk1 as an active ingredient.

Hereinafter, the present invention will be described in detail.

The processed Panax genus plant crude extract of the present invention is chopped the dried processed ginseng, about 1 to 20 times the weight (kg), preferably about 3 to 10 times the water, C1 to C4 lower alcohol or their Mixed solvent, preferably 70% ethanol, cold soaking, hot water extraction, for about 1 hour to 10 days, preferably about 2 hours to 5 hours, at an extraction temperature of 20 ° C to 100 ° C, preferably 50 ° C to 70 ° C, The extract obtained by the ultrasonic extraction, reflux cooling extraction method is filtered, concentrated under reduced pressure or lyophilized to obtain a crude extract as a polar solvent soluble extract.

In addition, the non-polar solvent soluble extract of the present invention, after suspending the crude extract in distilled water, the suspension is about 1 to 100 times, preferably about 1 to 5 times the volume of hexane, chloroform, methylene chloride, ether, ethyl acetate and The same nonpolar solvent can be added to obtain a non-polar solvent soluble layer 1 to 10 times, preferably 2 to 5 times, to be obtained by extraction and separation. It is also possible to further carry out conventional fractionation processes (Harborne JB Phytochemical methods: A guide to modern techniques of plant analysis. 3rd Ed. Pp 6-7,1998).

In a preferred embodiment of the present invention, the processed ginseng is refluxed with 70% ethanol to obtain a crude extract, which is extracted with ether to obtain an ether soluble extract and an aqueous extract, and then the aqueous extract is extracted with butanol. Fractions and aqueous fractions are obtained.

When the anti-anxiety effect was measured by administering the extract of the processed ginseng according to the present invention, it was confirmed that a significant anti-anxiety effect appeared in the butanol fraction of the processed ginseng.

The composition comprising Panax genus plant extract of the present invention may further comprise a suitable carrier, excipient and diluent according to conventional methods.

Carriers, excipients and diluents that may be included in the composition comprising the Panax genus plant extract of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, Alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. .

Compositions comprising Panax genus plant extract according to the present invention, respectively, according to a conventional method of oral formulations, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories and sterile injectable solutions It can be formulated and used in the form.

The amount of Panax genus plant extract of the present invention may vary depending on the age, sex, and weight of the patient, but may be administered once to several times in an amount of 0.1 to 100 mg / kg. In addition, the dosage of the Panax genus plant extract may be increased or decreased depending on the route of administration, the severity of the disease, sex, weight, age, and the like. Therefore, the above dosage does not limit the scope of the present invention in any aspect.

The composition comprising the plant extract of Panax genus of the present invention can be used in various formulations, such as drugs, foods and beverages for the prevention and treatment of anxiety-related diseases in the above formulation. The health functional food of the present invention is preferably in the form of a pharmaceutical or health beverage such as powders, granules, tablets, capsules, pills, suspensions, emulsions, syrups, aerosols. Examples of the food to which the Panax genus plant extract can be added include various foods, beverages, gums, teas, vitamin complexes, and health functional foods.

Panax genus plant extract of the present invention has little toxicity and side effects, so can be used with confidence even for long-term use for the purpose of prevention.

Panax genus plant extract of the present invention may be added to food or beverage for the purpose of prevention of anxiety-related diseases. At this time, the amount of the Panax plant extract in the food or beverage may be added at 0.01 to 15% by weight of the total food weight, the health beverage composition is 0.02 to 5 g, preferably 0.3 to 1g based on 100 ml Can be added.

The health functional beverage composition of the present invention is not particularly limited to other ingredients except for having the extract as an essential ingredient in the indicated ratio, and may contain various flavors or natural carbohydrates, etc. as additional ingredients, as in general beverages. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of said natural carbohydrate is generally about 1-20 g, preferably about 5-12 g per 100 ml of the composition of the present invention.

In addition to the above, the composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and salts thereof. , Organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. The compositions of the present invention may also contain pulp for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

The present invention is described in more detail based on the following examples, although the present invention is not limited thereto.

Example 1 Preparation of Special Processed Ginseng

Special processed ginseng was prepared by the method of the literature (Kim et al., Journal of Natural Products, Vol. 63, pp. 1702-1704, 2000; Vol., Et al., Journal of Chromatography A, Vol. 921, pp. 335-339, 2001). .

1 kg of ginseng was put into an autoclave and heated using steam at 120 ° C. for 3 hours. Take out the heat-treated ginseng and dried at 50 to 60 ℃ to prepare a processed ginseng of the present invention.

Example 2 Preparation of Special Processed Ginseng Extract

1 kg of specially processed ginseng was refluxed three times with 70% ethanol for 3 hours, after which the solvent was blown to obtain 350 g of specially processed ginseng extract.

Example 3 Preparation of Specially Processed Ginseng Fraction

300 g of the extract of Example 2 was suspended in 3 liters of water and extracted with ether, the ether layer was collected and the solvent was blown out to obtain an ether fraction 30 g, and the remaining aqueous layer was extracted with butanol to blow off the solvent from the butanol layer and the aqueous layer, respectively. 130 g of butanol fraction and 130 g of water fraction were obtained.

Comparative Example Preparation of Ginseng Extract

After cutting 1kg of white ginseng and refluxing three times with 70% ethanol for 3 hours, the solvent was blown out to prepare 310 g of white ginseng extract.

Example 5 Ginsenoside Content Analysis of Processed Ginseng

The ginseng saponin components contained in the special processed ginseng, raw white ginseng, and red ginseng prepared according to the present invention were analyzed by the following method.

The special processed ginseng prepared in Example 1 was pulverized into powder using a grinder, 1 g of each was taken into a 50 mL flask, and refluxed three times for 20 hours with 70 mL of ethanol to collect the extract. Each extract was concentrated by evaporation under reduced pressure, and the residue was dissolved in methanol to make 20 mL.

Separately, white ginseng and red ginseng purchased on the market were extracted in the same manner to prepare white and red ginseng samples.

As a result of analyzing each saponin component by HPLC using the ginsenoside Rb1 and Rg3 standard solutions by the method of literature (Kwon et al., Journal of Chromatography A, vol. 921, pp 335-339), the results are shown in Table 1 below.

As shown in Table 1, in the case of specially processed ginseng, the sum of (Rg3 + Rg5 + Rk1) is higher than the sum of (Rb1 + Rb2 + Rc + Rd).

Ginsenoside Relative Peak Area of Ginseng Rb1 Rb2 Rk1 Rc Rd Rg3 Rg5 (Rg3 + Rg5 + Rk1) / (Rb1 + Rb2 + Rc + Rd) Example 1 1.46 3.91 3.11 0.59 34.2 8.94 12.5 6.1 White ginseng 18.5 12.1 14.3 6.66 0 0 0 0 Red ginseng 16.3 9.05 11.4 5.34 1.05 0.55 0.34 0.046

Experimental Example 1 Anti-Anxiety Effect Measurement

ICR-based male mice (20-25 g) were used for the experiment, and 10-15 animals per group were used in the experiment. Ten animals per cage had a temperature (22 ± 2 ° C) and a light / dark cycle (12 hours light / dark cycle). It was used for the experiment after a certain breeding period in the animal room kept constant. Water and feed were adequately supplied during the experiment. Samples were dissolved or dissolved in physiological saline or DMSO and administered orally 3 hours before measurement.

Anti-anxiety effect was measured using a plus-maze. The plus-maze is made of black plexiglas, with two open arms (30 × 5 cm) and closed arms (30 × 5 × 15 cm) in opposite directions. The open arm has no railings and the closed arm is made of transparent plexiglass, 15 cm high. The plus-maze was placed 38 cm high from the bottom and used for the experiment.

The experiment allowed the mouse to roam freely in the middle of the maze, looking at the open arms. All test procedures were recorded and recorded with a video camera perpendicular to the maze. For 5 minutes, the number of times of entry into the open and closed arms and the length of stay in the open arm were measured and recorded. The measurement time spent in open arms relative to the total time spent in the plus-maze (300 seconds) was expressed as a percentage. All these experiments were carried out between 13: 30-16: 30 in a quiet environment with low noise (50 Lux). Entry is when all four feet are in an open or closed arm.

Significance test used Student's t-test statistical method.

Oral administration of white ginseng and specially processed ginseng extract at a dose of 50 mg / kg is shown in FIG. 1. As shown in Figure 1, the white ginseng administration group tended to increase compared to the control group administered only saline, but there was no significance. However, the special ginseng group showed significantly higher open cancer access than the control group or white ginseng group. In addition, as shown in FIG. 2, the time spent in open cancer was also significantly increased in the group treated with special ginseng. Through this, special processed ginseng showed strong anti-anxiety effect.

On the other hand, oral administration of the ether fraction, water fraction, and butanol fraction of specially processed ginseng at 25 mg / kg dose, respectively, showed no significant effect in the ether fraction and water fraction as shown in FIGS. 3 and 4. However, the butanol fraction showed a significant anti-anxiety effect. This butanol fraction is composed mainly of ginsenosides (20S) Rg3, (20R) Rg3, Rg5 and Rk1.

Specially processed ginseng is made by specially processing ginseng and the sum of the contents of ginsenosides Rg3, Rg5, and Rk1 is greater than the sum of the contents of ginsenosides, Rb1, Rb2, Rc, and Rd. In particular, it was found that butanol fraction mainly containing saponin contained anti-anxiety active ingredient.

The processed ginseng extract of the present invention may be administered in the following formulations, and the following formulation examples are merely to illustrate the present invention, thereby not limiting the contents of the present invention.

Formulation Example 1 Preparation of Tablet

Processed ginseng extract of Example 3 ............ 200 mg

Lactose 100 mg

Starch .............................. 100 mg

Magnesium Stearate ...............

The above components are mixed and tableted according to a conventional method for producing tablets to produce tablets.

Formulation Example 2 Preparation of Capsule

Processed Ginseng Extract of Example 4 ... 100 mg

Lactose 50 mg

Starch ........................................ 50 mg

Talc ........................................ 2mg

Magnesium Stearate ...............

Capsules are prepared by mixing the above ingredients and filling into gelatin capsules according to a conventional method for preparing capsules.

Formulation Example 3 Preparation of Liquid

Processed Ginseng Extract of Example 3 ................................... 1000 mg

Sugar ........................................ 20g

Isomerized sugar ......................................... 20g

Lemon Flavor ......................

Purified water was added to make a total of 1000 ml.

According to the conventional method for preparing a liquid, the above components are mixed, and then filled into a brown bottle and sterilized to prepare a liquid.

Formulation Example 4 Preparation of Healthy Food

Processed Ginseng Extract of Example 3 ...................................... 1000 mg

Vitamin Blend ...............

Vitamin A Acetate ......... 70 μg

Vitamin E ............ 1.0 mg

Vitamin B1 ........................ 0.13 mg

Vitamin B2 ........................ 0.15 mg

Vitamin B6 ............... 0.5 mg

Vitamin B12 ............... 0.2 μg

Vitamin C ............ 10 mg

Biotin .............................. 10 ㎍

Nicotinamide ......... 1.7 mg

Folic acid ......................... 50 μg

Calcium Pantothenate ......... 0.5 mg

Inorganic mixtures ...............

Ferrous Sulfate ............... 1.75 mg

Zinc Oxide ............... 0.82 mg

Magnesium Carbonate ............... 25.3 mg

Potassium monophosphate ......................................... 15 mg

Dibasic calcium phosphate ............... 55 mg

Potassium Citrate ............... 90 mg

Calcium Carbonate ... 100 mg

Magnesium Chloride ........................... 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method. The granules may be prepared and used for preparing a health food composition according to a conventional method.

Formulation Example 5 Preparation of Healthy Drink

The processed ginseng extract of Example 4 .. 1000 mg

Citric Acid .................................... 1000 mg

Oligosaccharide ......................................... 100 g

Plum concentrate ........................... 2 g

Taurine ......................................... 1 g

Purified water is added to the whole ..... 900 ㎖

After mixing the above components in accordance with a conventional healthy beverage production method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and then refrigerated and stored in the present invention For the preparation of healthy beverage compositions.

Although the composition ratio is a composition suitable for a preferred beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, use purpose.

The special processed ginseng according to the present invention is manufactured without mixing any chemicals with ginseng, so it can be used as an anxiety agent, antidepressant, or antistress agent with no side effects or toxicity.

Claims (6)

A pharmaceutical composition for preventing and treating anxiety symptoms containing a processed ginseng extract in which the active ingredient is increased so that the ratio of ginsenosides (Rg3 + Rg5 + Rk1) / (Rb1 + Rb2 + Rc + Rd) is 1.0 or more. The pharmaceutical composition according to claim 1, wherein the extract is soluble in water, C ₁ to C ₄ lower alcohols, or a mixed solvent thereof. The method of claim 1, wherein the ginseng is Panax ginseng , Panax quinquefolia , Panax ginseng , Panax notoginseng , Panax japonica , Panax trifolia , Panax pseudoginseng ), Panax vietnamensis , Panax elegatior , Panax wangianus , or Panax bipinratifidus , starch , root, stem, or leaf Pharmaceutical composition. An anti-anxiety agent comprising a processed ginseng butanol fraction containing (20S) Rg3, (20R) Rg3, Rg5, and Rk1 as main components. delete delete

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