KR20060000488A - Composition containing ginseng extract comprising saponin derivatives isolated from ginseng radix and ginseng for preventing and treating scratching diseases - Google Patents

Abstract

The present invention relates to a pruritus preventive or therapeutic composition containing as an active ingredient at least one ginseng extract selected from the group consisting of ginseng or red ginseng extract, its lactic acid bacteria fermentation product and enteric bacteria fermentation product or ginseng saponin derivative isolated therefrom. .

Red Ginseng Extract, Lactic Acid Bacteria Fermentation, Pruritus, Ginseng Saponin Derivatives

Description

Ginseng or Red Ginseng Extract, Lactic Acid Bacteria Fermentation thereof and one or more ginseng extracts selected from the group consisting of enteric bacteria fermentation. }

The present invention relates to a pruritus preventive or therapeutic composition containing as an active ingredient at least one ginseng extract selected from the group consisting of ginseng or red ginseng extract, its lactic acid bacteria fermentation product and enteric bacteria fermentation product or ginseng saponin derivative isolated therefrom. .

Pruritus, called itching, is a condition of the skin that causes the heart to scratch and is caused by contact with stimulants, rapid temperature changes, or mental stress, physical, chemical, electrical, or thermal stimuli. Especially when you are in a state of psychological anxiety or when you are afraid, you may feel severe itching and usually appear most severely before going to bed. The body is particularly sensitive to itching, and the external auditory meatus, eyelids, nostrils and vulva are known as sensitive areas.

The mechanism of occurrence of pruritus is related to chemicals such as histamine, kinin, protease, prostaglandin and the like. In addition, the degree of pruritus varies greatly depending on the person, and the same stimulus has a different response in the same person.

Currently known major pruritus include paroxysmal pruritus, which is a very severe, persistent and recurrent pruritis that occurs in bayonet simple tachycardia, atopic dermatitis, herpes dermatitis, and the like; Vulvar pruritus caused by psychogenic factors caused by scrotum pruritus, candidiasis, trichomoniasis vaginitis, pads, contraceptives, vaginal lavage fluid, condoms, and contact dermatitis, urinary incontinence, diabetes, sclerotic atrophic salivary glands in men; Herpes dermatitis, insect bites, scabies, atopic dermatitis, contact dermatitis, psoriasis, molecular eczema, chronic simple thyroiditis, nodular papules, systemic dermatitis, and the like.

In the treatment of pruritis, the use of appropriate topical agents, such as topical steroids, are often used and systemically administered antihistamines. However, these chemical synthetic therapies have serious side effects. There is a need in the art.

Accordingly, the present inventors also conducted a number of studies to develop a natural substance that can replace the chemically synthesized pruritus therapeutic agent having a serious side effect developed in the past, as a result, ginseng or red ginseng extract, its lactic acid bacteria fermentation and One or more ginseng extracts selected from the group consisting of enteric bacteria fermentation products or ginseng saponin derivatives isolated therefrom have a very excellent pruritus prevention and treatment effect, and they find that there are no side effects on the human body as natural substances and Completed.                         

Therefore, it is an object of the present invention to provide a novel pruritus prophylactic or therapeutic composition.

In order to achieve the above object, the composition according to the present invention is an active ingredient of one or more ginseng extract selected from the group consisting of ginseng or red ginseng extract, its lactic acid bacteria fermentation product and enteric bacteria fermentation product or ginseng saponin derivative separated therefrom It is characterized by containing.

More specifically, the composition according to the present invention, as a ginseng saponin derivative isolated from the ginseng extract, panaxitriol, panaxidol, panaxinol, ginsenoside Rc, ginsenosides Rb1, Rb2, ginsenosides Side Rg3, Compound K, Ginsenoside Rh2, 20 (R) -Ginsenoside Rh2, 20 (R) -Protopanaxadiol, 20 (S) -Ginsenoside Rh2, 20 (S) -Protopanaxadiol , 20 (S) -ginsenoside Rh1, at least one ginseng saponin derivative selected from the group consisting of 20 (S) -protofaxaxatriol, preferably in particular compound K, ginsenoside Rg3, ginsenoside Rh2 Provided is a composition for preventing and treating pruritus as an active ingredient.

Composition for the prevention and treatment of pruritus of the present invention, the ginseng extract and ginseng saponin derivative separated therefrom may comprise 0.02 to 90% by weight relative to the total weight of the composition.

As used herein, ginseng extract can often be used in the sense of containing ginseng or red ginseng extract itself, or the product obtained by fermenting the extract of ginseng or red ginseng itself by lactic acid bacteria or enterobacteriaceae. . Pruritus prevention or therapeutic composition according to the present invention is characterized in that it comprises ginseng extract in this comprehensive sense.

In addition, as used herein, ginseng saponin derivative means a medicinal ingredient included in the ginseng extract, not only saponins known in the art, but also included in the ginseng extract that may represent the medicinal ingredient. Unknown ginseng saponin derivatives are also included.

Hereinafter, the present invention will be described in more detail.

Panax ginseng CA Meyer is a perennial root of the genus Ginseng which belongs to the genus Oga and Ginseng according to the plant taxonomy. (1) Korean ginseng ( Panax ginseng CA Meyer) is located in the Far East of Asia (North 33 ~ 48 ㅀ: Korea, North Manchuria, It is native to parts of Russia and has very good efficacy. (2) American Ginseng ( Panax quinquefolium L.) grows and grows in the United States and Canada, and (3) Panax notoginseng FHChen is located in the southwestern region of Guangxi province in southeastern Yunnan Province, China. (4) Panax japonicus CA Meyer is known to be distributed in Japan, southwest China and Nepal (和 漢 藥 百科 圖鑑, Vol. 1, pp. 1-8, Nambatsunehik, Hoi An). Courier, 1980).

On the other hand, ginseng is classified into its form, which is divided into the form of fresh ginseng which is grown and harvested, white ginseng which is dried at room temperature, or red ginseng produced by heat-treating ginseng or white ginseng at 98-100 ° C.

These ginsengs have a lot of pharmacological effects that are soured as a commodity in the new agricultural herb. Many pharmacological experiments have been conducted to enhance the nonspecific resistance of ginseng to the stress of ginseng, to increase the anti-acidic effect, to improve hypertension, to increase insulin action, to lower the blood sugar in alloxan diabetic mice, to synthesize liver RNA in rats It has been found to have protein synthesis, sugar and lipid metabolism promoting effect, and anti-cancer effect. Also, it has been used for various diseases such as psychiatric disease, nervous system disease and diabetes in the form of herbal medicine, and saponin is the main component of ginseng Has been shown to be effective in tonic, gangjeong, sedation, hematopoietic and antihypertensive (Nambatsuneki et al., 和 漢 藥 百科 圖鑑, 1 , pp1-8, 1980).

Currently, the pharmacological efficacy of major ginsenoside components as saponins or derivatives thereof contained in ginseng has been found, and the results are shown in Table 1 below.

Kinds of Ginsenosides efficacy Ginsenoside-Rb1 Central and mental stability, central feeding, aggression, analgesia, anticonvulsion, anti-anxiety, adrenal cortex stimulating hormone and corticosterone secretion, cholesterol biosynthesis, memory improvement, high cholesterol and triglycerides Lowering of fatty acids, promoting neuronal survival, protecting liver injury, promoting DNA, RNA, protein and lipid synthesis of bone marrow cells, promoting the release of acylcholine, vasodilation, inhibiting platelet aggregation, inhibiting lipid peroxidation, promoting cholesterol metabolism, anti-inflammatory, Activation of phagocytosis, inhibition of renal glomeruli. Ginsenoside-Rb2 Promoting sugar and fat metabolism, antidiabetic action, maintaining nitrogen metabolism equilibrium, promoting protein and lipid synthesis, hypocholesterolemic and anti-arteriosclerosis, antagonism of cancer toxin hormone, inhibition of smooth muscle cell proliferation, DNA, RNA, corticosteroids and Promotes corticosterone secretion, improves stress appetite loss, suppresses tumor angiogenesis, promotes the production of antioxidant active substances, activates ATP supply of liver tissues, regulates cholesterol, promotes metabolism of cholesterol, promotes hepatocyte proliferation and DNA synthesis, suppresses platelet aggregation, and analgesic effect Ginsenoside-Rc Promotes liver, serum cholesterol and RNA synthesis, promotes bone marrow cell DNA, RNA, protein and lipid synthesis, analgesics, corticosteroid secretion, prostacyclin biosynthesis, renal glomerular hypertrophy Ginsenoside-Rd Adrenal cortex stimulating hormone and corticosteroid secretion, renal glomeruli hypertrophy Ginsenoside-Re Stimulation of adrenal cortical stimulation hormone and corticosteroid, analgesic, vasodilation, anti-hot stress, smooth muscle cell proliferation, myeloid cell DNA, RNA, protein and lipid synthesis, protection of liver injury, cholesterol metabolism Ginsenoside-Rg1 Immune function, platelet aggregation inhibition, antithrombin, good activation, memory and learning function, anti-fatigue, anti-stress, central excitement, vasodilation, anti-inflammatory, anti-nephritis and renal blood flow, high temperature environment and endogenous fever Protective action against harmful stimuli, improvement of stress slow-acting disorder, promotion of neuronal survival rate, promotion of hepatocyte proliferation and DNA synthesis, promotion of adrenal cortex stimulating hormone secretion, promotion of cholesterol metabolism, protection of liver damage Ginsenoside-Rh1 Experimental anti-inflammatory effect, tumor cell differentiation promotion, platelet aggregation inhibition, glandular activation activity, anti-inflammatory effect, anti-allergic effect Ginsenoside-Rh2 Inhibition of cancer cell proliferation, promotion of cancer cell regeneration, inhibition of cancer cell infiltration, inhibition of tumor growth, enhancement of anticancer activity of anticancer agents, anti-allergic effect, anti-inflammatory effect Compound K Potent tumor angiogenesis and cancer cell metastasis inhibition, type IV collagenase secretion, anti-angiogenic activity and platelet aggregation inhibition, anti-allergic effect, anti-allergic effect, anti-inflammatory effect

As is currently known, ginsenosides, the main component of the pharmacological efficacy of ginseng, are saponins of Rb1, Rb2 and Rc. However, the component K (20-0-β-D-glucopyranosyl-20 (S) -protopa, which is substantially contained in ginseng, contains a component that substantially inhibits anticancer action or cancer metastasis of cancer cells or antiallergic action. incident diol), ginsenoside Rh1 and Rh2 seed, and the Δ ²⁰ - it is known that the saponin component of the seeding ginsenoside Rh2. For use for anti-cancer activity, anti-allergic effect, immune enhancing action of ginseng, compounds K, ginsenosides Rh1 and Rh2 contained in the ginseng, and Δ ²⁰ -ginsenoside Rh2 (with ginsenoside Rk2 and It is known to increase the content of the saponin component of the ginsenoside Rh3).

However, none of the previously reported literature describes any disclosure or teaching that ginseng containing compositions may be effective in treating and preventing pruritus.

According to the present invention, at least one ginseng extract selected from the group consisting of ginseng or red ginseng extract, its lactic acid bacteria fermentation product and its enterobacterial fermentation product, or ginseng saponin derivative isolated therefrom, and a saponin derivative isolated therefrom, compound K, gin Cenoside Rf, Ginsenoside Rg3, Ginsenoside Rh2 and the like have been found to be effective in the prevention and treatment of pruritus (itch).

According to the present invention, when ginseng is prepared using conventional methods known in the art and extracts are obtained, ginsenosides Rg3 may be obtained a lot, but the compounds K and ginsenosides Rh2 It was found that the increase in saponin component was not significant. In addition, according to the present invention, a significant increase of compound K was observed when the ginseng or red ginseng extract was fermented, but no significant increase in the ginsenoside Rh2 component was observed in the lactobacillus fermented extract of ginseng. Significant increase of ginsenoside Rh2 component was observed only in lactic acid bacteria or enteric bacteria fermented extracts.

Hereinafter, a method for preparing ginseng extract included in the pruritus prevention or therapeutic agent composition according to the present invention will be described in detail. However, the production method described below is not particularly limited, and red ginseng production method and lactic acid bacterium fermentation method known in the art may also be applied to the present invention.

(1) washing and drying process

In order to remove foreign substances contained in ginseng, fresh ginseng is washed with water, optionally 0.1% acetic acid and dried. The use of acetic acid-containing water may be desirable because it is effective in removing contaminating bacteria.

(2) Preparation of Red Ginseng

The ginseng washed in the above (1) is steamed at 98-100 ° C. for 1 to 10 hours, preferably 2 to 5 hours, and 60 ° C. for 5 hours using a red ginseng manufacturer. Red ginseng can be obtained by drying using a dryer. Conditions and additional matters necessary for the preparation of other red ginseng are commonly known in the art, and red ginseng that can be used in the preparation of the red ginseng extract according to the present invention can be prepared by performing such known application. .

(3) extraction process

20 to 80 ° C., preferably using about 1 to 50 times (weight / volume) of water, alcohol or a mixture of water and alcohol (preferably 70% alcohol) to dry white or red ginseng including fresh ginseng Extraction and concentration at a temperature of 50 to 60 ° C. for 1 to 2 days, preferably 3 hours, extracts the saponin component contained in ginseng or red ginseng.

Ginseng that can be applied to the extraction process, including ginseng and ginseng processed products and by-products, preferably ginseng, red ginseng, white ginseng, rice ginseng, ginseng leaves, ginseng extract and ginseng in powder form. Extracts of this type of ginseng may optionally be used in the following bioconversion processes.

(4) bioconversion process

Lactobacillus or enteric bacteria were added to concentrated suspensions of fresh ginseng, white ginseng, red ginseng water extract or 70% alcohol extract for 20 hours to 50 ° C, preferably 25 to 40 hours for 6 to 5 days, preferably 24 to 48 hours. Cultured at a temperature of ℃ to obtain a biologically fermented ginseng fermentation. At this time, the fermentation period and the fermentation temperature may be appropriately selected in consideration of the strain used and the extraction efficiency.

(5) concentration or lyophilization process

The ginseng fermented extract obtained by the above step (4), specifically white ginseng or red ginseng fermented extract may be used as it is or may be used after lyophilization. Alternatively, the supernatant may be extracted by water or alcohol and used after drying. Such concentration or lyophilization methods are commonly known in the art.

In this series of manufacturing process, the manufacturing process of red ginseng causes ginsenoside-Rb1, ginsenoside-Rb2, ginsenoside-Rc, etc., which are contained in ginseng, to be converted into ginsenoside Rg3, and lactic acid bacteria or intestines Bacterial bioconversion may be such that ginsenoside-Rg3 obtained in the preparation of red ginseng is converted to the final metabolite ginsenoside Rh2. By bioconversion of white ginseng or fresh ginseng, ginsenoside-Rb1, ginsenoside-Rb2, and ginsenoside-Rc are converted only to compound K.

The lactic acid bacteria that can be used for the bioconversion may be any one that can metabolize ginseng saponin to produce the ginsenoside Rh2, preferably, lactic acid bacteria of the Bifidobacterium genus, more preferably. Preferably Bifidobacterium infantis, Bifidobacterium Bifiduum, Lactobacillus lactis, Clostridium butyricum, Bifidobacterium H- 1 (KCCM), Bifidobacterium KK-1, Bifidobacterium KK-2, Bifidobacterium KK-11 (Kim Hee University, Kyung Hee University Pharmacy Kim Dong-Hyun Professor) One or a mixture of these may be used.

The intestinal bacteria that can be used for the above-mentioned bioconversion can also be any one that can also metabolize ginseng saponin to produce the compound K or ginsenoside Rh2, preferably in the genus Bacterioides, Fusobac Intestinal bacteria of the genus Fusobacterium, Eubacterium, more preferably bacterioid JY-6 (Kim, Hee University College of Medicine, Biol. Pharm. Bull. , 23 , pp1481-1485, 2000), Fusobac Terium K-60 (Professor, Dong-Hyun Kim, Kyung Hee University, Biol. Pharm. Bull. , 23 , pp1481-1485, 2000), Yoobacterium L-8 (Professor, Dong-Hyun Kim, Kyung Hee University, Biol. Pharm. Bull. , 23 , pp1481- 1485, 2000).

On the other hand, according to the present invention, the step (5) is an optional step, and if the steps (1) and (2) are carried out, the steps (3) and (4) are essential continuous manufacturing steps, and the step (4) The red ginseng extract and the strain may be prepared by encapsulating the mixture without culturing so that the reaction can occur in the human intestine, and if the red ginseng manufacturing process is not performed, that is, without the step (2), the step (1) is performed. In this case, the processes (3) and (4) may be performed immediately, and all these processes may be selectively applied according to the form of the final ginseng product.

In addition, the following process may be further performed.

A freeze-drying step of concentrating or freeze-drying the ginseng extract of the step (5) as it is;

Centrifuging the ginseng extract of step (5), filtering the supernatant, and concentrating the filtrate under reduced pressure to remove impurities and precipitates in the bioconverted ginseng extract of step (3) and concentrating at the same time, followed by a drying process such as lyophilization. Fermentation process;

As an extraction process to extract only the active ingredient contained in the ginseng extract of step (5) with a suitable solvent, using a lower alcohol solution such as water, methanol and ethanol as a suitable solvent, and special supercritical extraction method An extraction step of separating the active ingredient using an extraction method, and a drying step by a lyophilization method subsequent thereto;

Stirring or dilution process for preparing processed beverages or processed foods.

The ginseng extract of the present invention obtained by performing all of the above manufacturing steps (1) to (4), including the manufacturing process of red ginseng is (ginsenoside Rh2 + compound K) / (ginsenoside Rg3 + Rc + Rd + The ratio of Rb1 + Rb2) may be at least 0.1.

On the other hand, the ginseng extract of the present invention obtained without the red ginseng manufacturing process, i.e., immediately after the manufacturing process (1) was performed, was subjected to the manufacturing processes (3) and (4) (compound K + ginsenoside Rd) / (gin The ratio of cenosides Rc + Rd + Rb1 + Rb2) may be at least 0.1.

In the present invention, the ginseng fermentation extract obtained by performing all the above production steps (1) to (4) was extracted with Concentrated BuOH and concentrated, followed by silica gel column (5 × 50 cm, elution solvent: chloroform: methanol = 20: 1). Can be used to separate ginsenosides Rh2; Without the red ginseng manufacturing process, that is, the extract obtained by performing the manufacturing processes (3) and (4) immediately after the manufacturing process (1) is carried out, the compound K can be separated under the same conditions as above.

Hereinafter, the application form of the pruritus prevention or therapeutic agent composition which concerns on this invention is demonstrated concretely.

The antipruritic or therapeutic composition according to the present invention comprising one or more ginseng extracts selected from the group consisting of ginseng or red ginseng extract, its lactic acid bacteria fermentation product and its enterobacterial fermentation product or ginseng saponin derivative isolated therefrom as an active ingredient, If it does not adversely affect the pruritic prevention or treatment effect, it can be processed into various forms of ginseng products currently marketed in the art, by containing any additional material or performing any process.

Such ginseng products include, but are not particularly limited to, ginseng dry powders, extracts, ampoule preparations, teas, tablets and the like.

In addition, compositions comprising extracts or compounds of the invention may be formulated as pharmaceutically acceptable pharmaceutical formulations, further comprising suitable carriers, excipients and diluents according to conventional methods.

Carriers, excipients and diluents which may be further included in a composition comprising the extract of the present invention or a saponin derivative contained therein as an active ingredient 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.

In addition, the composition comprising the extract of the present invention or a saponin derivative contained therein as an active ingredient, respectively, oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc. It may be used in the form of external preparations, suppositories and sterile injectable solutions or in cosmetic materials such as soap.

The amount of the extract of the present invention or the saponin derivative contained therein may vary depending on the age, sex and weight of the patient, but the amount of 0.1 to 100 mg / kg may be administered once to several times daily. In addition, the dosage of the extract or compound 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 extract of the present invention or a saponin derivative contained therein may be used in various forms such as pharmaceuticals, food, beverages and cosmetics for the prevention and treatment of pruritus as described above. Foods to which the ginseng extract of the present invention or saponin derivative contained therein can be added, for example, various foods, beverages, gums, teas, vitamin complexes, health supplements, soaps and the like.

The ginseng extract and the compound of the present invention have little toxicity and side effects, and thus are drugs that can be used safely even for prolonged administration for the purpose of prevention.

The extract of the present invention or saponin derivative contained therein may also be added to food, beverage or cosmetics for the purpose of preventing pruritus. At this time, the amount of the extract or saponin derivative contained in the present invention, in the case of health supplements or cosmetics can generally be added in an amount of 0.01 to 15% by weight based on the total weight of the composition, in the case of drinks, 100 ml Can be added at a ratio of 0.02 to 20 g, preferably 0.1 to 1 g (dry weight).

The health food or beverage composition according to the invention may optionally further contain various flavors or natural carbohydrates and the like in the indicated proportions. Examples of such 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. In addition, natural flavors (tauumatin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavoring agents. The proportion of carbohydrates is generally about 0.1-20 g, preferably about 0.5-5 g (dry weight) per 100 ml (100 g) of the composition of the present invention.

Compositions according to the present invention include various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic and natural flavors, colorants and neutralizers (such as cheese, 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. In addition, the compositions of the present invention may further 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 limited, 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.

On the other hand, the effect on the pruritus of the composition according to the present invention is azelastine (commercial drug) in an in vivo test using a pruritus model animal induced with compound 48/80, histamine, substance P, etc. Can be confirmed as an effect of suppressing pruritus.

The method was evaluated by injecting compound 48/80, histamine, substance P into the blood of a mouse and measuring the behavior (scraping, licking, etc.) for 1 hour, and the sample was intraperitoneally administered 1 hour before. Or 3 hours before oral administration can be used to determine the inhibitory effect of the itch.

Hereinafter, the present invention will be described in more detail based on the following examples, but the present invention is not limited thereto.

Example 1 Preparation of Raw Ginseng Extract (1)

Cut 20 g of 5 year old ginseng purchased from Geumsan Ginseng Market, add 5 times the amount of water, extract it at 60 ℃ for 5 hours, concentrate it under reduced pressure with a concentrator (Eyella, KN-IN Evaporator, Japan), and freeze-drier (three-way cold heat SFDSM24L). Model, Korea) to obtain 1 g of raw white ginseng dry powder.

Example 2 Preparation of Processed Ginseng Extract (2)

1 kg of 5 year old ginseng purchased from Geumsan Ginseng Market was washed with water (in some cases, the washing process may be added with 0.1% acetic acid), and steamed at 98-100 ° C. for 4 hours and dried at 60 ° C. for 5 hours. This dried red ginseng was extracted with 70% alcohol to obtain a red ginseng extract. This was concentrated, suspended in water, extracted with BuOH and concentrated to obtain a red ginseng extract.

Example 3 Preparation Example of Ginseng Fermented Extract (3)

1 kg of 5 year old ginseng purchased from Geumsan Ginseng Market was washed with water and extracted with 70% alcohol to obtain white ginseng extract. This white ginseng extract was suspended in sterile distilled water to 0.5%, added Bifidobacterium H-1 strain (wet weight 10 grams), incubated for 24 hours at 37 ° C., extracted with BuOH, concentrated, and processed. 4 g of ginseng was obtained.

Example 4 Preparation Example of Red Ginseng Fermented Extract (4)

1 kg of 5 year old ginseng purchased from Geumsan Ginseng Market was washed with water and finally washed with acetic acid containing 0.1%, steamed at 98-100 ° C for 4 hours and dried at 60 ° C for 5 hours. This dried red ginseng was extracted with 70% alcohol to obtain a red ginseng extract. The red ginseng extract was suspended in sterile distilled water so as to be 0.5%, Bifidobacterium H-1 strain (wet weight 10 g) was added thereto for 24 hours, incubated at 37 ° C. for 72 hours, extracted with BuOH and concentrated to Lactic acid bacteria fermented product 4g was obtained.

Example 5 Preparation Example of Red Ginseng Enterobacteriaceae Fermented Extract

1 kg of 5 year old ginseng purchased from Geumsan Ginseng Market was washed with water and finally washed with 0.1% acetic acid and steamed at 98-100 ° C. for 4 hours and dried at 60 ° C. for 5 hours. This dried red ginseng was extracted with 70% alcohol to obtain a red ginseng extract. This red ginseng extract was suspended in sterile distilled water to 0.5%, and enterobacterial fungus (10 g of cell weight obtained by suspending fresh feces in tryptic soy broth) was added for 37 hours. After culturing at 72 ° C. for 72 hours, the mixture was extracted with BuOH and concentrated to obtain 4 g of enteric bacteria fermentation of red ginseng.

Example 6 Preparation of Compound K from Enteric Bacteria Fermentation of Ginseng

1 kg of 5 year old ginseng purchased from Geumsan Ginseng Market was washed with water and extracted with 70% alcohol to obtain ginseng extract. This ginseng extract was suspended in sterile distilled water to 1%, and enteric bacteriophage (10 g of cell weight obtained by suspending fresh feces in tryptic SoybroTm) was incubated at 37 ° C for 72 hours for 24 hours. After extraction, the resultant was extracted with BuOH and concentrated to obtain 15 g of processed ginseng, which was eluted with silica gel curl (5 × 50 cm, eluting solvent, chloroform: methanol = 20: 1) to separate 0.6 g of Compound K.

Example 7 Preparation of Ginsenosides Rg3 and Rh2 from Enteric Bacteria Fermentation of Red Ginseng

1 kg of 5 year old ginseng purchased from Geumsan Ginseng Market was washed with water and finally washed with acetic acid containing 0.1%, steamed at 98-100 ° C for 4 hours and dried at 60 ° C for 5 hours. This dried red ginseng was extracted with 70% alcohol to obtain a red ginseng extract. This red ginseng extract was suspended in sterile distilled water to 1%, and enteric bacteriophage (10 g of cell weight obtained by suspending fresh feces in tryptic soy broth) was added and incubated at 37 ° C for 72 hours for 72 hours. Then, extracted with BuOH and concentrated to obtain a processed ginseng 12 g, which was eluted with silica gel curl (5 x 50 cm, eluting solvent, chloroform: methanol = 20: 1) 0.3 g of ginsenoside Rg3 and 0.2 g of ginsenoside Rh2 was isolated.

Example 8. Content Analysis Experiment

2 g each of the raw ginseng of Example 1 and the powders of the extracted ginseng BuOH extracted fractions of Examples 2, 3 and 4 were taken 2 g each and suspended in 100 ml of water, and extracted three times with 100 ml of ether and concentrated under reduced pressure. Then, the resultant was extracted three times with 100 ml of butanol and concentrated under reduced pressure, and the obtained concentrate was dissolved in 100 ml of methanol to obtain 100 mg of saponin fraction, which was then purified by TLC (developing solvent: CHCl ₃ : MeOH: H ₂ O = 65: 35: 10, Coloring reagent: 5% methanolic acid sulfate solution, Detector: Shimadzu TLC Scanner CS-9301PC) to obtain the saponin content analysis results as shown in Table 2.

ingredient Content in Saponin Fraction (%) Example 1 Example 2 Example 3 Example 4 Ginsenoside Rb1 13.4 5.8 2.8 2.9 Ginsenoside Rb2 8.9 3.4 1.9 1.8 Ginsenoside Rc 9.2 1.7 1.5 1.4 Ginsenoside Rd 3.3 1.0 1.1 1.3 Ginsenoside Rg3 <1 5.7 <1 2.7 Δ ²⁰ -ginsenoside Rg3 <1 1.1 <1 <1 compound K <1 <1 5.2 2.9 Ginsenoside Rh2 <1 <1 <1 1.8 Protopananacidio Diol <1 <1 <1 <1

As shown in Table 2, red ginseng obtained by steaming ginseng has a sharp increase in ginsenoside Rg3 content compared to white ginseng, and compound K increased when the ginseng was fermented with lactic acid bacteria or enterobacteriaceae. The content of ginsenoside Rh2 in which ginsenoside Rg3 was metabolized rapidly increased.

Example 1: Cultivation Behavior Test

The cultivation behavior test was performed according to the Sugimoto method (Eur. J. Pharmacol., 351, 1-5, 1998). Before the experiment, five groups of BALB / c mice (compound 48/80, experimental animal models for use by serotonin and substance P) and ICR mice (experimental animal models for histamine induction) were used. After standing for 10 minutes at 24 x 22 x 24 cm, the hair on the cervical back is removed, and then a 29-gauge needle is used for the antipruritic agent (50 μg of Compound 48/80 (Sigma, USA), or 100 μg of histamine ( Sigma, USA), or 300 μg of serotonin (Sigma, USA), or 100 μg of Substance P (Sigma, USA), physiological saline administered as a normal control, and then immediately placed into the observation box. One by one was isolated and recorded for 1 hour with 8-mm video (SV-K80, Samsung) under unattended conditions and observed the results. It was admitted that scratching the injection site with the hind paw was not permitted. In order to evaluate the efficacy of ginseng extract and saponin isolated therefrom, the experimental materials were intraperitoneally injected 1 hour before the induction drug or 6 hours before oral administration. One group of animals was used in 5 animals.

The results are shown in Table 3 below.

Treatment Sample Capacity (mg / kg) % Inhibition Oral administration Intraperitoneal administration Compound 48/80 Induction Compound 48/80 Induction Histamine induction Serotonin induction Substance P Induction Example Sample 1 50 34 - - - - Example Sample 2 50 32 - - - - Example Sample 3 50 34 - - - - Example Sample 4 50 44 - - - - Example Sample 5 50 45 - - - - Ginsenoside Rb1 10 28 55 47 49 43 Ginsenoside Rb2 10 30 48 40 38 - Ginsenoside Re 10 26 51 41 40 - Ginsenoside Rg1 10 30 63 51 48 - Ginsenoside Rf 10 31 65 59 61 - Ginsenoside Rg3 10 15 70 68 89 - Ginsenoside F1 10 22 68 65 72 - Ginsenoside Rh2 10 29 60 58 65 -  Ginsenoside Rh1 10 27 55 58 62 - Compound K 10 41 73 74 93 77  Protopananacidio Diol 10 22 45 35 38 - Azelastine (positive control) 5 45 65 75 47 77

As shown in Table 3, ginseng saponins showed the most anti-pruritic effect, and among them, the compound K and the ginseng fermented extract showed a better effect. Among the saponins, compound K showed the most excellent effect. Therefore, ginseng extract and saponin derivatives isolated therefrom were found to have an effective effect on skin pruritus.

Experimental Example 2; Capillary Permeability Inhibition

It is known that capillary permeability is increased at the site of pruritus induction, and thus, this experiment was performed to see if the extract according to the present invention can effectively eliminate the capillary permeability induced by various compounds.

Capillary permeability experiment with Compound 48/80 was carried out according to the Sugimoto method (Eur. J. Pharmacol., 351, 1-5, 1998) using 5 mice per group, such as the animals used in the above experiment. That is, 50 μg of Compound 48/80 was injected subcutaneously into the cervical back region, and then 0.2 ml of 1% Evans blue solution (Sigma, USA) was administered intravenously, and then lethal, and Compound 48/80 was administered. The skin of one site was cut and placed in 1 ml of 1N KOH, and then reacted at 37 ° C the next day. Then, 4 ml of a mixed solution of 0.6N phosphate-acetone (5:13) was added and mixed, followed by mixing at 3000 rpm for 15 minutes. After centrifugation, the supernatant was taken and the absorbance was measured at 620 nm. The drug used was the same as the practication experiment. The results are shown in Table 4 below.

Treatment Sample Capacity (mg / kg) % Inhibition Oral administration Intraperitoneal administration Compound 48/80 Induction Compound 48/80 Induction Histamine induction Example Sample 1 50 32 - - Example Sample 2 50 30 - - Example Sample 3 50 28 - - Example Sample 4 50 40 - - Example Sample 5 50 37 - - Ginsenoside Rb1 10 25 50 - Ginsenoside Rb2 10 26 47 - Ginsenoside Re 10 29 48 - Ginsenoside Rg1 10 20 - - Ginsenoside Rf 10 25 - - Ginsenoside Rg3 10 10 - - Ginsenoside F1 10 35 61 - Ginsenoside Rh2 10 25 58 -  Ginsenoside Rh1 10 26 45 - Compound K 10 35 63 54  Protopananacidio Diol 10 15 - - Azelastine (positive control) 5 - 65 34

In this table, the inhibition rate was calculated as follows.

% Inhibition = {1- [absorbance of the extract and compound 48/80 (or histamine) treated site according to the present invention-absorbance of the compound 48/80 (or histamine) untreated site] / [compound 48/80 (Or histamine) absorbance at site treated with Compound 48/80 (or histamine) at site not treated]} × 100 = inhibition rate (%)

As shown in Table 4, the results of the practicability test showed an effect of oral administration, intraperitoneal administration or capillary permeability. In particular, compound K showed excellent effects, and both ginseng and fermented products of ginseng showed excellent effects. This effect had the effect of suppressing pruritus.

Hereinafter, a pharmaceutical formulation for preventing or treating pruritus of the present invention will be described in detail.

Formulation Example 1 Preparation of Powder

According to the preparation method of powder in the pharmacopeia formulation, it is prepared in the following ingredient content per one packet.

Dry powder of any one of Examples 1 to 4 50 mg

Lactose · ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ 100 mg

Talc 10 mg

Formulation Example 2 Preparation of Tablet

According to the preparation method of tablets in the pharmacopeia formulation, it is prepared in the following component content per tablet.

Dry powder of any one of Examples 1 to 4 50 mg

Corn starch ㆍ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ 100 mg

Lactose · ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ 100 mg

Magnesium Stearate 2 mg

Formulation Example 3 Preparation of Capsule

According to the preparation method of capsules in the pharmacopeia formulation, it is prepared in the following component content per capsule.

Dry powder of any one of Examples 1 to 4 50 mg

Corn starch ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ 100 mg

Lactose ····················· 100 mg

Magnesium stearate 2 mg

Formulation Example 4 Preparation of Liquid

According to the preparation method of the liquid formulation in the Pharmacopoeia General Formulation, it is prepared in the following component content per 100 ml of the liquid formulation.

Dry powder in any one of Examples 1 to 4 ... 50 mg

Heterosaccharides ················· 10 g

Mannitol ···················· 5 g

Purified water ㆍ ···················

Formulation Example 5 Preparation of Soap

Soap is prepared in component content according to a general manufacturing method.

Dry powder of any one of Examples 1-4 ..... 0.05-2 g

Palm oil (other oils) ・ ・ ・ ・ ・ ・ ・ ・ 100 g

NaOH or KOH 15 g (20 g)

Purified water ㆍ ···················

In addition, it is possible to manufacture a health beverage in the following manner.

0.1 to 80% of dry powder of any one of Examples 1 to 4, 5 to 10% of sugar, 0.05 to 0.3% of citric acid, 0.005 to 0.02% of caramel, 0.1 to 1% of vitamin C and mixed with 79 to 94 Make syrup by mixing% purified water, sterilize the syrup at 85 ~ 98 ℃ for 20 ~ 180 seconds, mix with cooling water at a ratio of 1: 4, and then inject processed carbon dioxide 0.5 ~ 0.82% A carbonated beverage containing a dry extract was prepared.

Example 1 Homogeneous sterilization by homogeneous mixing of dry powder and subsidiary materials such as liquid fructose (0.5%), oligosaccharide (2%), sugar (2%), salt (0.5%) and water (75%) Healthy drinks were prepared by packaging in small packaging containers such as glass bottles and plastic bottles.

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

As described above, the composition according to the present invention, ginseng or red ginseng extract, its lactic acid bacteria fermentation product and enteric bacteria fermentation product of at least one ginseng extract selected from the group consisting of or ginseng saponin derivative separated therefrom as an active ingredient By containing it, it can be usefully used as a pruritic prevention or therapeutic agent composition.

Claims (8)

A pruritus preventive or therapeutic composition comprising ginseng or red ginseng extract, its lactic acid bacteria fermentation product and enteric bacteria fermentation product thereof, as one or more ginseng extracts or ginseng saponin derivatives isolated therefrom as an active ingredient. The ginseng saponin derivative of claim 1, wherein the ginseng saponin derivative is panaxitriol, panaxidol, panaxinol, ginsenoside Rc, ginsenosides Rb1, Rb2, ginsenoside Rg3, compound K, ginsenoside Rh2, 20 (R) -ginsenoside Rh2, 20 (R) -protopanaxadiol, 20 (S) -ginsenoside Rh2, 20 (S) -protopanaxadiol, 20 (S) -ginsenoside Rh1, 20 (S)-Protopanaxatriol and ginsenoside Rf is at least one ginseng saponin derivative selected from the group consisting of pruritus prevention or treatment composition. The method of claim 1, wherein the lactic acid bacteria used for lactic acid bacteria fermentation of ginseng or red ginseng extract are bifidobacterium or Lactobacillus genus lactic acid bacteria. The method according to claim 1, wherein the enterobacteria used for enteric bacteria fermentation of ginseng or red ginseng extract are Bacterioides strain, Fusobacterium strain, Eubacterium strain and human or mammal Pruritus prevention or therapeutic agent composition selected from the group consisting of mixed strains of bacteria parasitic in the intestine of the body. Pharmaceutical products comprising ginseng or red ginseng extract, one or more ginseng extracts selected from the group consisting of lactic acid bacteria fermentation products and enteric bacteria fermentation products thereof, or ginseng saponin derivatives isolated therefrom, and pharmaceutically acceptable excipients, carriers or carriers. Preparations. A health supplement comprising at least one ginseng extract selected from the group consisting of ginseng or red ginseng extract, its lactic acid bacteria fermentation product and its enterobacterial fermentation product, or a ginseng saponin derivative isolated therefrom, and a food acceptable additive. Cosmetics comprising ginseng or red ginseng extract, one or more ginseng extracts selected from the group consisting of lactic acid bacteria fermentation products and enteric bacteria fermentation products thereof, or ginseng saponin derivatives isolated therefrom, and pharmaceutically acceptable excipients, carriers or carriers. . Soap comprising one or more ginseng extracts selected from the group consisting of ginseng or red ginseng extract, its lactic acid bacteria fermentation product and enteric bacteria fermentation product or ginseng saponin derivative isolated therefrom.