WO2020209702A1 - Composition for ameliorating, treating, or preventing skin diseases comprising echinacea purpurea juice - Google Patents

Abstract

The present invention relates to a composition for ameliorating, treating, or preventing allergic or inflammatory skin diseases. More specifically, the composition comprises Echinacea purpurea juice as an active ingredient, and thus relieves edema of the ears of an inflammatory skin disease animal model and reduces the levels of whole white blood cells, neutrophils, eosinophils, blood IgE, and the like in a blood test, and accordingly, can be used as a pharmaceutical composition for treating or preventing allergic or inflammatory skin diseases, a pharmaceutical composition for use in animals for treating or preventing allergic or inflammatory skin diseases, a food composition for ameliorating allergic or inflammatory skin diseases, or a feed composition for ameliorating allergic or inflammatory skin diseases.

Description

Composition for improving, treating, or preventing skin diseases containing the juice of Jaju Cheonin Guk

The present invention relates to a composition for improving, treating or preventing skin diseases, particularly allergic or inflammatory skin diseases, and more particularly, a pharmaceutical composition for the treatment or prevention of allergic or inflammatory skin diseases comprising the juice of Jasper Cheonin Guk as an active ingredient , It relates to a pharmaceutical composition for animals for the treatment or prevention of allergic or inflammatory skin diseases, a food composition for improving allergic or inflammatory skin diseases, or a feed composition for improving allergic or inflammatory skin diseases.

Human skin consists of the dermis and epidermis. In particular, the epidermis, located at the outermost part of the skin, protects against various stimuli from the outside, such as physicochemical stimuli such as chemicals, air pollutants, dry environments, and ultraviolet rays, and prevents excessive release of body moisture through the skin. It performs a protective function of preventing.

Among the epidermis, the outermost stratum corneum is formed from keratinocytes, and consists of keratinocytes that have been differentiated and the lipid layer surrounding them. Keratinocytes are eliminated from the skin after a certain period of time, and new keratinocytes raised from the lowermost layer of the epidermis take over their function.These repetitive processes of change are called epidermis differentiation or keratinization. . In the process of keratinization, keratinocytes form a stratum corneum while generating natural moisturizing factor (NMF) and intercellular lipids, making the stratum corneum firm and flexible, acting as a barrier to the outside as a skin barrier. You will have the function.

The stratum corneum may easily lose its function due to excessive washing, lifestyle factors such as bathing, environmental factors such as dry air pollutants, and endogenous diseases such as atopic skin or senile skin. In fact, in modern times, as harmful factors to the skin are gradually increasing, the rate of formation and dropout of the stratum corneum is slowed due to changes in dietary habits, and the amount of moisturizing factors and lipids in the stratum corneum decreases due to the decline in the function of keratinocytes. There is an increasing trend of people with skin whose stratum corneum does not function as a normal skin barrier.

In particular, atopic dermatitis is an allergic or inflammatory skin disease that has a high risk as the prevalence of atopic dermatitis increases rapidly in recent years.It is estimated that it is related to genetic factors and immune system deficiency, but the exact cause has not yet been identified. It is expected to be somewhat alleviated through improvement of diet, but there is no fundamental treatment method.

It has been found that atopic dermatitis causes IgE to be produced in mast cells in the process of removing allergens that have come into contact with or in the body, and if it comes into contact with or comes in with the same allergens, the human body becomes hypersensitive to allergens. As a result, histamine is produced, leading to atopic dermatitis.

As the treatment for atopic dermatitis, steroid topical drugs, antihistamines, calcineurin inhibitors, antibiotics, and ultraviolet therapy have been mainly used.However, in the case of long-term use, skin atrophy, capillary dilation, etc. A reaction has occurred and there is a limitation due to various side effects such as a risk of inducing adrenal suppression, so there are relatively few side effects and interest in new treatments capable of treating atopic dermatitis is increasing.

On the other hand, Echinacea purpurea is a perennial plant of the Asteraceae family, native to North America, and is widely cultivated for ornamental purposes all over the world because of its gorgeous flowers, and is also used as a remedy for colds and various viral infections by enhancing immunity.

[Prior technical literature]

[Patent Literature]

Korean Patent Publication No. 2016-0128589

Korean Patent Registration No. 1891218

Korean Patent Registration No. 1302222

The problem to be solved by the present invention is to provide a pharmaceutical composition for the treatment or prevention of allergic or inflammatory skin diseases, comprising the juice of Jasper Cheonin Guk as an active ingredient.

Another problem to be solved by the present invention is to provide a pharmaceutical composition for animals for the treatment or prevention of allergic or inflammatory skin diseases, comprising the juice of Jagalcheonin Guk as an active ingredient.

Another problem to be solved by the present invention is to provide a food composition for improving allergic or inflammatory skin diseases, including the juice of Jajucheonin-guk as an active ingredient.

Another problem to be solved by the present invention is to provide a feed composition for improving allergic or inflammatory skin diseases, including the juice of Jagalcheoninguk as an active ingredient.

The present invention provides a pharmaceutical composition for the treatment or prevention of allergic or inflammatory skin diseases, comprising the juice of Jagalcheonin Guk as an active ingredient in order to achieve the above object.

According to an embodiment of the present invention, the allergic or inflammatory skin disease is skin inflammation, eczema, contact dermatitis, atopic dermatitis, seborrheic dermatitis, chronic lichen planus, intermittent dermatitis, deprived dermatitis, papular urticaria, psoriasis, psoriatic arthritis. , Sun dermatitis, sunburn and acne may be any one of the skin diseases selected from.

According to an embodiment of the present invention, the self-made heaven-in-guk may be a stem, leaf, or above-ground outpost of the self-made heaven-in-guk.

According to an embodiment of the present invention, the pharmaceutical composition may be an oral formulation.

According to an embodiment of the present invention, the oral preparation may be a powder, granule, tablet, capsule, troche, suspension, emulsion, syrup or aerosol.

In addition, the present invention provides a pharmaceutical composition for animals for the treatment or prevention of allergic or inflammatory skin diseases, comprising the juice of Jasper Cheon In Guk as an active ingredient.

In addition, the present invention provides a food composition for improving allergic or inflammatory skin diseases, including the juice of Jajucheonin-guk as an active ingredient.

According to an embodiment of the present invention, the food composition may be a powder, granule, tablet, capsule, pill, extract, jelly formulation, tea bag formulation, or beverage formulation.

According to an embodiment of the present invention, the food composition may be a health functional food for improving allergic or inflammatory skin diseases.

In addition, the present invention provides a feed composition for improving allergic or inflammatory skin diseases, comprising the juice of Jagalcheoninguk as an active ingredient.

In addition, the present invention provides a method for treating allergic or inflammatory skin diseases in which the composition is orally administered to humans or animals other than humans.

In addition, the present invention provides a novel use of the juice for the treatment of allergic or inflammatory skin diseases, or for the manufacture of veterinary medicine.

The composition for improving, treating, or preventing allergic or inflammatory skin diseases comprising the juice of Jasper Cheonin Guk as an active ingredient of the present invention reduces swelling of the ear in an animal model of inflammatory skin disease, and in blood tests, total leukocytes, neutrophils, eosinophils, As it reduces the level of IgE, pharmaceutical compositions for treating or preventing allergic or inflammatory skin diseases, pharmaceutical compositions for animals for treating or preventing allergic or inflammatory skin diseases, food compositions for improving allergic or inflammatory skin diseases, or allergic or It can be used as a feed composition for improving inflammatory skin diseases.

Hereinafter, the present invention will be described in detail.

The inventors of the present invention evaluated the level of total leukocytes, neutrophils, eosinophils, blood IgE, etc. in ear edema and blood tests by orally administering Jagal Cheonin Guk juice in an allergic or inflammatory skin disease animal model. As a result, it was confirmed that the oral administration of Jajucheonin-guk juice has a remarkable therapeutic effect on allergic or inflammatory skin diseases.

The present invention relates to a pharmaceutical composition for the treatment or prevention of allergic or inflammatory skin diseases, comprising a juice juice of Jagalcheoninguk as an active ingredient.

In addition, the present invention relates to a pharmaceutical composition for animals for the treatment or prevention of allergic or inflammatory skin diseases, comprising the juice of Jagalcheoninguk as an active ingredient.

The term'juice liquor' as used in the present invention refers to a juice obtained by compressing, pulverizing and compressing the stem, leaves, or above-ground outposts, fractions fractionated from them, concentrates obtained by additionally concentrating these juices or fractions, Purified or separated purified product is also included, and the juice, fraction, concentrate, or purified product is dried or dried or pulverized.

In order to prepare 1 part by weight of the Jasper Cheonin Guk juice powder, about 20 to 100 parts by weight, preferably 30 to 60 parts by weight of undried Jasper Cheoninguk juice, and 1 part by weight of the Jasper Cheon In Guk juice powder 10 to 50 parts by weight of the liquid, preferably 15 to 30 parts by weight, are required.

For the preparation of the purified product, various additionally carried out, such as passing through an ultrafiltration membrane having a molecular weight cut-off value, or separation by various chromatography (made for separation according to size, charge, hydrophobicity or affinity) Purification methods can be added.

The Jagal Cheonin Guk juice is remarkably effective in treating allergic or inflammatory skin diseases compared to the aqueous extract of Jagal Cheonin Guk using water, alcohol having 1 to 4 carbon atoms or a mixed solvent thereof, or a fat-soluble extract fractionated with hexane, ethyl acetate, etc. outstanding.

The juice of the Jasper Cheonin Guk may be a juice of leaves, stems of Echinacea purpurea , or the above-ground outposts including the same, but the efficacy of reducing allergic or inflammatory skin diseases by oral administration is excellent.

The term'allergic or inflammatory skin disease' used in the present invention may include, without limitation, skin diseases that moisturize an allergic or inflammatory reaction occurring in the skin, for example, skin inflammation, eczema, contact dermatitis, atopic dermatitis. , Seborrheic dermatitis, chronic lichen planus, interstitial, deprived dermatitis, papular urticaria, psoriasis, psoriatic arthritis, sun dermatitis, sunburn and acne, preferably any one skin disease, preferably chronic refractory allergic or It may be atopic dermatitis, an inflammatory skin disease.

The'pharmaceutical composition','pharmaceutical','veterinary pharmaceutical composition', or'veterinary medicine' is an active ingredient, in addition to the juice of Jasper Cheonin Guk, a suitable carrier, excipient, and diluent commonly used in the manufacture of pharmaceutical compositions, etc. Can include.

The'carrier' is a compound that facilitates the addition of the compound into cells or tissues. The'excipient' is a compound added to provide an appropriate form to the active ingredient to be formulated or to increase the amount for convenient use. The'diluent' is a compound that is diluted in water to dissolve the compound as well as stabilize the biologically active form of the target compound.

The carrier, excipient, and diluent do not need to be particularly limited, but for example, lactose, glucose, sugar, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose , Methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.

The amount of use of the pharmaceutical composition, medicament, veterinary pharmaceutical composition or veterinary medicament may vary depending on the age, sex, and weight of the patient or the animal to be treated, and above all, the condition of the subject to be treated, a specific category of the disease to be treated, or It will depend on the type, route of administration and the nature of the therapeutic agent used.

The pharmaceutical composition, medicament, veterinary pharmaceutical composition or veterinary medicament is appropriately selected according to the absorption of the active ingredient in the body, the excretion rate, the age and weight, sex and condition of the patient or the animal to be treated, and the severity of the disease to be treated. , In general, it is preferred to administer 10 to 5,000 mg per day, preferably 50 to 4,000 mg, more preferably 100 to 3,000 mg, and most preferably 200 to 2,000 mg per day. The unit dosage form formulation thus formulated may be administered several times at regular time intervals as needed.

The pharmaceutical composition, medicament, veterinary pharmaceutical composition, or veterinary medicament may be individually administered as a prophylactic or therapeutic agent, or may be administered in combination with other therapeutic agents, and may be administered sequentially or simultaneously with a conventional therapeutic agent.

The pharmaceutical composition, medicament, veterinary pharmaceutical composition, or veterinary medicament is formulated and used in oral preparations such as powders, granules, tablets, capsules, troches, suspensions, emulsions, syrups, aerosols, etc., according to a conventional method. I can. In the case of formulation, it can be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, troches, and the like, and such solid preparations include at least one excipient for the compound, such as starch, calcium carbonate, sugar or lactose, gelatin. It can be prepared by mixing and the like. In addition, in addition to simple excipients, lubricants such as magnesium stearate and talc may be used. Liquid preparations for oral use include suspensions, liquid solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweetening agents, fragrances, and preservatives may be included. .

The treatment method of the allergic or inflammatory skin disease is to orally administer the composition to humans or non-human animals, especially mammals, for example, oral administration of the composition to an individual to be treated with an allergic or inflammatory skin disease. It is to administer.

The dosage, administration method, and number of administrations for the treatment may refer to the dosage, administration method, and number of administrations of the pharmaceutical composition, medicine, veterinary pharmaceutical composition or animal medicine.

The present invention relates to a food composition for improving allergic or inflammatory skin diseases, comprising the juice of Jajucheoninguk as an active ingredient.

The'food composition' includes food ingredients and food additives described in the Code of Food Additives, which can be used as foods described in the standards and standards of foods commonly used in food manufacturing ('Food Code'), in addition to the juice juice of Jasper Cheonin Guk as an active ingredient. Can include.

The food composition is not particularly limited, but may include, for example, carbohydrates and flavoring agents. The carbohydrates include monosaccharides such as glucose and fructose; Disaccharides such as maltose, sugar, lactose, and the like; Oligosaccharides or polysaccharides such as dextrin, starch syrup, cyclodextrin, and the like; Sugar alcohols such as xylitol, sorbitol, erythritol, and the like can be used. The flavoring agent may be a natural flavoring agent [taumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.)] and a synthetic flavoring agent (saccharin, aspartame, etc.).

In the case of preparing a food composition using the juice of Jagalcheoninguk as an active ingredient, the juice of Jagaloninguk does not need to be particularly limited as long as it has an effect of improving allergic or inflammatory skin diseases, but, for example, 0.1 to 99% by weight, 0.5 to It may be included in 95% by weight, 1 to 90% by weight, 2 to 80% by weight, 3 to 70% by weight, 4 to 60% by weight, 5 to 50% by weight.

In the food composition, the juice juice of Jajucheonin-guk, which is an active ingredient, varies depending on the condition, weight, and the presence or absence of disease and the duration of the ingestion, but may be appropriately selected by a skilled person. For example, it may be 10 to 5,000 mg, preferably 50 to 4,000 mg, more preferably 100 to 3,000 mg, most preferably 200 to 2,000 mg per day, based on the daily dosage, and the number of administration is particularly Although it does not need to be limited, it can be adjusted by a person skilled in the art within the range of 3 times a day to once a week. In the case of long-term intake for the purpose of health and hygiene or for the purpose of health control, it may be less than the above range.

The food composition is not particularly limited, but may be, for example, a powder, a granule, a tablet, a capsule, a pill, an extract, a jelly formulation, a tea bag formulation, or a beverage formulation.

In addition, in order to impart the function of improving allergic or inflammatory skin diseases to general foods, the juice of Jagalcheoninguk may be added. Foods that can be added do not need to be particularly limited, but for example, confectionery, bread or rice cakes, processed cocoa products or chocolates, meat, etc. as exemplified in the food standards and standards ('Food Code') according to Article 7 of the Food Sanitation Act. Egg processed products, processed fish products, tofu or jelly, noodles, tea, coffee, beverages, special purpose foods, pastes, seasoned foods, dressings, kimchi, salted fish, pickles, stewed foods, alcoholic beverages, raisins, and other foods. Can be. In addition, it may be added to dairy products, processed meat products and packaged meats, and egg products exemplified in the processing standards and ingredient specifications of livestock products according to Article 4 of the Livestock Hygiene Management Act ('Livestock Products Code').

On the other hand, the food composition containing the juice of Jaju Cheonin Guk as an active ingredient is a health functional food for improving allergic or inflammatory skin diseases, for example, a health functional food for improving atopic dermatitis, "health functional food that helps alleviate hyperimmune reactions" Or, it may be used as "health functional food that helps improve skin condition due to immune hypersensitivity reaction".

The'health functional food' refers to a food manufactured (including processing) in accordance with legal standards using raw materials or ingredients having useful functions for the human body (Article 3, No. 1 of the Health Functional Food Act). The'health functional food' may differ in terms or ranges from country to country, but'Dietary Supplement' in the United States,'Food Supplemnet' in Europe,'Health Functional Food' in Japan or ' It may correspond to'Food for Special Health Use (FoSHU)' and'Health Food' in China.

The food composition or health functional food may additionally contain food additives, and the suitability as a food additive shall be determined according to the standards and standards for the relevant item in accordance with the general rules and general test methods of the'Food Additive Code' unless otherwise specified. Follows.

In addition, the above health functional foods are'functional raw materials' used in "health functional foods that help alleviate hyperimmune reactions" or "health functional foods that help improve skin conditions due to immune hypersensitivity reactions" together with Jagal Cheonin Guk juice. As a raw material notified as or individually approved, Enterococcus feacalis heat-treated dry powder, guava leaf extract and other complexes, saffron extract, lobular extract, picaopreto powder, and other complexes, synthetic PLAG, L. sakei Probio 65, oil containing gammarinolenic acid , Fruit and vegetable-derived lactic acid bacteria ( L. plantarum CJLP133), probiotics ATP, and other health functional food materials related to relieving hyperimmune reactions can be used in combination.

The present invention relates to a feed composition for improving allergic or inflammatory skin diseases, comprising the juice of Jagalcheoninguk as an active ingredient.

The'feed composition' can be used as an active ingredient, as well as food ingredients and food additives listed in the Food Additives Code, which can be used as foods specified in the standards and standards of food ('Food Code'), in addition to the juice of Jasper Cheonin Guk. Even if it is not a possible food raw material or food additive, raw materials that fall within the range of sweet feeds in Appendix 1 of'Standards and Specifications for Feed, etc.' and raw materials that fall within the range of auxiliary feeds in Appendix 2 can be used.

The'feed composition' may be an extractant among auxiliary feeds according to'standards and standards for feed, etc.', and may be a blended feed including the auxiliary feed.

In the case of preparing a feed composition using the juice of Jagalcheoninguk as an active ingredient, the juice of Jagalcheoninguk does not need to be particularly limited as long as it has an effect of improving allergic or inflammatory skin diseases, but, for example, 0.1 to 99% by weight, 0.5 to It may be included in 95% by weight, 1 to 90% by weight, 2 to 80% by weight, 3 to 70% by weight, 4 to 60% by weight, 5 to 50% by weight.

In the feed composition, the juice of Jagalcheonin-guk, which is an active ingredient, varies depending on the condition, weight, and the presence or absence of disease and the duration of the ingested animal, but may be appropriately selected by a person skilled in the art. For example, 1 to 5,000 mg, preferably 5 to 2,000 mg, more preferably 10 to 1,000 mg, even more preferably 20 to 800 mg, most preferably 50 to 500 mg, based on daily dosage It may be, the number of administration is not particularly limited, but can be adjusted by a skilled person within the range of 3 times a day to once a week. In the case of long-term intake for the purpose of health and hygiene or for the purpose of health control, it may be less than the above range.

Hereinafter, the present invention will be described in more detail with reference to preferred embodiments. However, these examples are for describing the present invention in more detail, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not limited thereto.

Experimental Example 1

1. Preparation of experimental animals and samples

Fingelberg's "Model No.: 0 347 318; Echinacea dried pressed juice (95% native)" was purchased and used as an EPJ powder. The Judge Cheonin Guk juice (EPJ) powder was dried from the juice obtained by extracting the outpost, and the JJJJJJ juice juice had a solid content of 95% by weight.

As a positive control group 1,'Styria extract', which is notified as a'functional raw material' used for "health functional food that helps alleviate hyperimmune reaction," was purchased and used. The edible extract was a brown powder, and the solid content of the extract was 41% by weight.

'Dexamethasone Tablet (DEX)' was purchased and used as a positive control group 2. The dexamethasone tablet is a white round tablet containing 0.5 mg of dexamethasone per sugar.

Experimental animals were supplied with Nc/Nga mice (4 weeks old, male) from Japan SLC, Inc., Japan and used. NC/Nga mice show a pattern of atopic dermatitis accompanied by overproduction of IgE, clinically and histologically, very similar to the lesions of human atopic dermatitis, and there are many cases that have been used as atopic dermatitis animal models. I chose.

Sufficient supply of solid feed and water, temperature 23±2 ℃, relative humidity 55±10%, ventilation frequency 10 to 20 times/hr, 12 hours to 12 hours (light-dark cycle) and illuminance 150 to 300 Lux. Breed.

Before the start of breeding, the auricle and the back of the neck of NC/Nga mice were depilated with a razor, and then, an appropriate amount of a depilatory agent was applied to remove the hair. Before administration of the test substance, atopic dermatitis-inducing reagent (Biostir AD, Biostir Inc., Japan) was applied to the back of the auricle, neck, and forelimbs 4 times in total on days 1, 5, 8 and 12 to induce atopic dermatitis. Evenly applied. On the 14th day, the skin clinical index was evaluated and distributed in a random method so that the average level of each group was distributed as uniformly as possible according to the ranked levels of atopic dermatitis.

In order to continuously induce atopic dermatitis even after the start of administration of the test substance, atopic dermatitis-inducing reagent was applied to the auricle, neck, and forelimb locations a total of 10 times on days 15, 19, 22, 26, 29, 33, 36, 40, 43 and 47. It was evenly applied to the back of the body.

All animal testing procedures were performed in compliance with NIH (National Institutes of Health)'s Principle of Laboratory Animal Care.

As shown in Table 1 below, group 1 of them induces atopic dermatitis for 2 weeks in the normal control group, and the remaining 4 groups induce atopic dermatitis for 2 weeks. Group 3 is 200 mg/kg based on the solid content of the juice extract excluding excipients, Groups 1-4 are 200 mg/kg based on the solid content of the extract of'Styria extract', and Groups 1-5 are the active ingredient of'Dexamethasone' 2 mg/kg was administered orally once a day based on a 10 mL/kg dose. The normal control group and the negative control group were orally administered 10 mL/kg of physiological saline as a vehicle.

division	Explanation
Group 1-1	Normal control, does not cause atopic dermatitis, physiological saline
Group 1-2	Negative control, atopic dermatitis induced, physiological saline
Group 1-3	Induces atopic dermatitis, JJJJ (EPJ) 200 mg/kg
Group 1-4	Positive control group 1, induces atopic dermatitis, Styria extract 200 mg/kg
Group 1-5	Positive control group 2, induced atopic dermatitis, dexamethasone 2 mg/kg

2. Weight measurement result

Initiation of atopic dermatitis induction 1, 14, 28, 42 and 49 Days body weight (g) was measured and shown in Table 2.

division	Group 1-1	Group 1-2	Group 1-3	Group 1-4	Group 1-5
Day 1	22.34±1.52	22.10±0.77	21.66±1.28	21.22±1.64	21.24±0.80
Day 14	25.90±1.85	25.57±0.95	25.40±2.16	24.47±2.02	24.54±0.99
Day 28	27.65±1.77	26.25±1.31	24.72±1.97 *	24.81±2.51 *	23.26±0.88 ***,##
Day 42	28.44±2.02	26.55±1.17	26.18±2.36	25.79±2.54	23.37±1.11 ***,#
Day 49	29.98±2.29	27.67±1.23	27.17±2.07	26.33±2.46 **	24.19±1.32 ***,##

Significant differences between the normal control group of group 1-1 and group 1-2 to group 1-5 were * p<0.05, ** p<0.01, *** p<0.001; Significant differences between the negative control group 1-2 and groups 1-3 to 1-5 were statistically significant across all test groups on the 14th day of the onset of atopic dermatitis induction, # p<0.05, ## p<0.01. No body weight difference was observed.

On the 28th day of the onset of atopic dermatitis (day 14 of test substance administration), the body weights of all test substance-administered groups 1-3 to 1-5 were significantly lower than that of the normal control group 1-1 (p<0.05). , p<0.05 and p<0.001), in particular, the body weight of group 1-5 to which dexamethasone was administered was significantly lower than that of group 1-2, which is the negative control group (p<0.01).

The body weight of groups 1-5 that were administered dexamethasone on the 42nd day of the onset of atopic dermatitis (day 28 of test substance administration) was significantly lower than that of the normal control group of group 1-1 (p<0.001) and group 1-2. Was significantly lower than that of the negative control group (p<0.01).

On the 49th day (day 35 of test substance administration) on the onset of atopic dermatitis induction, the body weight of groups 1-4 that were administered sativa extract was significantly lower than that of the normal control group of group 1-1 (p<0.01). Groups 1-5 were significantly lower than those of group 1-1 as well as group 1-2 (p<0.001 and p<0.01).

Significant weight loss in groups 1-5, which appeared from day 28 to day 49 of the onset of atopic dermatitis, was evaluated as a side effect of systemic administration of immunosuppressants. Since no significant difference was observed compared to group 1-2 in most of the dates, it was evaluated not due to the administration of the test substance.

3. Ear edema measurement result

Initiation of atopic dermatitis induction 1, 14, 28, 42, and 49 Primary ear thicknesses (mm) were measured with a caliper to confirm the occurrence of ear edema, and are shown in Table 3.

division	Group 1-1	Group 1-2	Group 1-3	Group 1-4	Group 1-5
Day 1	0.32±0.02	0.31±0.01	0.32±0.02	0.33±0.01	0.32±0.02
Day 14	0.33±0.02	0.40±0.06	0.42±0.11	0.42±0.09	0.47±0.17
Day 28	0.33±0.01	0.70±0.12 ***	0.60±0.19 **	0.61±0.09 **	0.45±0.11 ##
Day 42	0.33±0.01	0.89±0.09 ***	0.81±0.24 ***	0.73±0.10 ***	0.40±0.09 ###
Day 49	0.33±0.01	0.93±0.11 ***	0.82±0.25 ***	0.75±0.10 ***	0.43±0.10 ##

Significant differences between the normal control group of group 1-1 and group 1-2 to group 1-5 were * p<0.05, ** p<0.01, *** p<0.001; Significant differences between the negative control group 1-2 and groups 1-3 to 1-5 were # p<0.05, ## p<0.01, as atopic dermatitis was continuously induced. From the 14th day of administration of the substance) to the end of the test, the ear thickness levels of all atopic-induced groups except for groups 1-5 were significantly higher than in group 1-1 (p<0.001, p<0.01, or p<0.05), The ear thickness level of group 1-5 was significantly lower than that of the negative control group of group 1-2 (p<0.001 or p<0.01).

Compared to the negative control group of Group 1-2, the ear thickness of the group 1-3 administered with the extract of Jajucheonin-guk showed a tendency to decrease somewhat compared to the negative control group of Group 1-4, and showed a similar tendency to that of the group 1-4 administered with the extract.

4. Spleen weight measurement result

On the day of necropsy on the 49th day of the initiation of atopic dermatitis, the spleen was removed and the weight was measured, and the weight and the ratio to the body weight were shown in Table 4.

division	Group 1-1	Group 1-2	Group 1-3	Group 1-4	Group 1-5
Weight(g)	29.98±2.29	27.67±1.23	27.17±2.07	26.33±2.46	24.19±1.32
Spleen weight (g)	0.0856±0.0086	0.1143±0.0300	0.0842±0.0276	0.0964±0.0230	0.0283±0.0028 ***,###
Spleen weight to weight ratio (%)	0.2854±0.0182	0.4112±0.0941	0.3122±0.1095	0.3666±0.0812	0.1169±0.0109 **,###

Significant differences between the normal control group of group 1-1 and group 1-2 to group 1-5 were * p<0.05, ** p<0.01, *** p<0.001; Significant differences between the negative control group of group 1-2 and the group 1-3 to group 1-5 were # p<0.05, ## p<0.01 of group 1-2 compared to the normal control group of group 1-1. Both the absolute and relative spleen weights of the negative control group were increased, but among the test substance administration groups of groups 1-3 and 1-4, there was no statistically significant reduction in spleen weight compared to group 1-2. .

However, in the case of the dexamethasone-administered group of group 1-5, both absolute and relative weight levels of the spleen were significantly lower than those of groups 1-1 and 1-2 (p<0.001 and p<0.01), and In the case, it was found to be only about 25% of the level compared to group 1-2, indicating that the strong immunosuppressive effect of dexamethasone led to the contraction of the spleen.

5. Total leukocyte, neutrophil, eosinophil and IgE measurement results

Using the blood collected on the day of necropsy on the 49th day of the initiation of atopic dermatitis, the total white blood cell count was measured with an automatic cell count calculator (TC20 Automated Cell Counter, Biorad), and neutrophils and eosinophils were measured by flow cytometry. Was measured, and the IgE concentration in blood was measured by ELISA assay, and is shown in Table 5.

division	Group 1-1	Group 1-2	Group 1-3	Group 1-4	Group 1-5
Total white blood cells (x10 3 cells/µl)	1.75±0.34	11.03±5.06 ***	6.30±4.75 *,#	9.73±3.36 *	2.79±1.25 ##
Neutrophils (x10 3 cells/µl)	0.02±0.01	0.39±0.28 ***	0.11±0.05 #	0.26±0.32 *	0.05±0.01 ##
Eosinophil (ㅧ10 2 cells/µl)	0.01±0.00	0.43±0.18 ***	0.11±0.07 ###	0.25±0.25 **,#	0.04±0.01 ###
IgE (㎍ / ㎖)	0.1809±0.0709	11.0609±1.9891 ***	7.2643±2.7700 ***,###	9.5996±3.3080 ***	2.4256±0.7861 ###

Significant differences between the normal control group of group 1-1 and group 1-2 to group 1-5 were * p<0.05, ** p<0.01, *** p<0.001; The significant difference between the negative control group 1-2 and the group 1-3 to group 1-5 was # p<0.05, ## p<0.01, as a result of measuring the total white blood cell count, Only in the juice-treated group and the dexamethasone-treated group of group 1-5, the total leukocyte level was significantly lower than that of the negative control group of group 1-2 (p<0.05 and p<0.01).

In the case of neutrophils, the negative control group of group 1-2 and the group 1-4 treated with stalk extract were significantly higher than that of the positive control group of group 1-1 (p<0.001 and p<0.05). In group 3, the group administered with the juice solution of Jagalcheonin-guk and the group administered with dexamethasone in groups 1-5 were significantly lower than those in the negative control group in group 1-2 (p<0.01 and p<0.05).

In addition, in the case of eosinophils, the negative control group 1-2 and the group 1-4 administration group were significantly higher than the positive control group 1-1 (p<0.001 and p<0.01). -The group 3 administered with the juice of Jinghui Cheonin Guk and the group 1-5 administered with dexamethasone were significantly lower than those of the negative control group 1-2 (p<0.001 and p<0.001).

The group 1-3 administered with the extract of Jajucheonin-guk significantly reduced both neutrophils and eosinophils, which play an important role in the pathologic mechanism of atopic dermatitis, and was particularly superior to the group 1-4 treated with styrofoam extract. And, it was confirmed to be at a similar level to the dexamethasone-administered group of groups 1-5 of the positive control group 2.

On the other hand, blood IgE concentration was significantly higher in all atopy-inducing groups except for groups 1-5 than in the normal control group of group 1-1 (p<0.001), but the group 1-3 group administered the juice and The dexamethasone administration group of group 1-5 was significantly lower than that of the negative control group of group 1-2 (p<0.001 and p<0.001). From the above results, it was confirmed that the juice of Jajucheonin-guk of Group 1-3 is very effective in inhibiting the production of IgE, a key factor in allergic reactions.

Experimental Example 2

1. Preparation of experimental animals and samples

An additional experiment was conducted to compare the treatment effect of Jajucheonin-guk juice and Jajucheonin-guk extract on atopic dermatitis according to the administration route of Jajucheonin-guk juice.

The same powder as in Experimental Example 1 was used. As for the water extract (EPE), the extract obtained by extracting the dried product of Echinacea purpurea outpost with water at 100°C was used. The solid content of the water extract (EPE) was 4.9% by weight. In the same manner as in Experimental Example 1,'dexamethasone tablet (DEX)' was purchased and used as a positive control (positive control 2) for oral administration. 'Protopic ointment 0.1% (tacrolimus hydrate)' was purchased and used as a positive control for transdermal administration (positive control 3). 0.1% of the protopic ointment is a white to pale yellow ointment containing 1.02 mg/g of tacrolimus hydrate.

Experimental animals, breeding conditions, and methods of inducing atopic dermatitis were all performed in the same manner as in Experimental Example 1. However, in order to continuously induce atopic dermatitis after the start of administration of the test substance, atopic dermatitis-inducing reagent was applied to the back of the auricle, neck and forelimbs for a total of 8 times until day 15, 19, 22, 26, 29, 33, 36 and 40. It was applied uniformly, and an autopsy was performed on the 42nd day. As shown in Table 6 below, group 1 of them induces atopic dermatitis for 2 weeks in the normal control group, and the other 6 groups induce atopic dermatitis for 2 weeks. Group 3 is administered 200 mg/kg orally based on the solid content of the juice extract excluding excipients, Group 2-4 is administered orally 200 mg/kg based on the solid content of the extract, and Group 2-5 is the active ingredient of'dexamethasone'. 2 mg/kg was administered orally once a day based on a 10 mL/kg dose. The normal control group and the negative control group were orally administered 10 mL/kg of physiological saline as a vehicle.

In addition, groups 2-6 were transdermally administered 200 mg/kg to the atopy-induced back area at 10 mL/kg/day based on the solid content of the juice extract excluding excipients, and group 2-7 was administered 0.1% Protopic Ointment. It was administered transdermally at 100 mg/mari/day.

division	Explanation
Group 2-1	Normal control, does not cause atopic dermatitis, physiological saline, oral
Group 2-2	Negative control, induces atopic dermatitis, physiological saline, oral
Group 2-3	Induces atopic dermatitis, JJV extract (EPJ) 200 mg/kg, oral
Group 2-4	Causes atopic dermatitis, Jasper Cheonin Guk Water Extract (EPE) 200 mg/kg, oral
Group 2-5	Positive control group 2, inducing atopic dermatitis, dexamethasone 2 mg/kg, oral
Group 2-6	Causes atopic dermatitis, JJJJ juice extract (EPJ) 200 mg/kg, transdermal
Group 2-7	Positive control group 3, induces atopic dermatitis, Protopic ointment 100 mg/horse, dermal

2. Results of measuring the ratio of lymphocytes, eosinophils and basophils in the blood

The percentage of leukocytes was confirmed using the blood collected on the day 42 of necropsy on the 42nd day of induction of atopic dermatitis. The ratio of lymphocytes, eosinophils and basophils using an automatic blood analyzer (ADVIA 2120, SIEMENS, USA) after injecting some of the collected blood into a CBC bottle containing an anticoagulant EDTA-2K It is shown in Table 7 to confirm.

division	Lymphocytes (%)	Eosinophil (%)	Basophil (%)
Group 2-1	56.8±8.8	1.9±0.5	0.5±0.5
Group 2-2	58.7±9.2	8.2±6.9 **	0.5±0.3
Group 2-3	38.8±12.4 **,##	1.4±0.5 ###	0.2±0.1
Group 2-4	45.3±13.3	2.6±2.4 ##	0.6±0.4
Group 2-5	41.8±7.9 *,#	2.1±1.6 ##	0.2±0.2
Group 2-6	68.3±9.3	2.0±1.3 ##	0.4±0.5
Group 2-7	62.3±11.1	1.6±0.6 ##	0.2±0.2

Significant differences between the normal control group of group 2-1 and groups 2-2 to 2-7 were * p<0.05, ** p<0.01; Significant differences between the negative control group of group 2-2 and groups 2-3 to group 2-7 were # p<0.05, ## p<0.01, ### p<0.001, and the proportion of lymphocytes was group 2-5. It was significantly lower in the oral administration group of positive control group 2 and the oral administration of JJV juice (EPJ) of group 2-3 (p<0.01 and p<0.05). On the other hand, there was no significant difference in the oral administration group of Jagalcheoninguk water extract (EPE) of group 2-4, and also did not show a significant difference in the transdermal administration group of Jagalcheoninguk juice (EPJ) of group 2-7.

In atopic dermatitis, the number of inflammation-related cells, in particular, the ratio of eosinophils is increased, and eosinophils are known to play an important role in the pathological mechanisms of atopic dermatitis. The proportion of eosinophils was significantly increased in the oral administration group of the negative control group 2-2 compared to the oral administration group of the normal control group 2-1 (p<0.01), and in groups 2-3 to 2 It was significantly decreased in group 7 compared to the negative control group of group 2-2 (p<0.01, p<0.001),

Among them, the oral administration group of Epjeong-in-guk juice (EPJ) of group 2-3 was the oral administration group of EPE-dosed water extract (EPE) of group 2-4, and the transdermal administration of EPJ of group 2-7 Of course, compared to the positive control group 2 of group 2-5 and the positive control group 3 of group 2-7, the proportion of eosinophils was significantly reduced (p<0.001).

The proportion of basophils did not show any significant difference between the groups, but the oral administration group of JJV (EPJ) in group 2-3, positive control group 2 in group 2-5, and positive control group 3 in group 2-7. Showed a relatively low ratio compared to other groups.

Therefore, when administered orally, the ratio of lymphocytes and eosinophils was significantly reduced when administered orally, and when administered orally, the ratio of lymphocytes and eosinophils was significantly reduced when administered orally. It was confirmed that it was more effective in ordering.

Statistical analysis

The experimental results of Experimental Example 1 and Experimental Example 2 are expressed as mean ± standard deviation, and in the case of parametric multiple comparison, the normality of the data was assumed, and the result was tested by a parametric one-way variance analysis (One-way ANOVA). If is significant, a post-test was performed using Dunnett's multiple comparison test to analyze significant differences between test groups. In the case of nonparametric multiple comparisons, the test was performed with the Kruskal-Wallis'H-test, and if the result was significant, the significant difference between the test groups was analyzed using the post-analysis Mann-Whitney U test.

Statistical analysis was performed using Prism 7.04 (GraphPad Software Inc., San Diego, CA, USA), and a p value of less than 0.05 was determined to be statistically significant.

Hereinafter, an example of the formulation of a composition comprising the juice of the Jajucheonin-guk of the present invention is described, but the present invention is not intended to limit it, but is intended to be described in detail.

Formulation Example 1: Preparation of powder

Juju Cheonin Guk Juice (EPJ) Powder 20 mg

100 mg lactose

10 mg of talc

The above ingredients are mixed and filled in an airtight cloth to prepare a powder.

Formulation Example 2: Preparation of tablets

Juju Cheonin Guk Juice (EPJ) Powder 10 mg

100 mg corn starch

100 mg lactose

2 mg of magnesium stearate

After mixing the above ingredients, tablets are prepared by tableting according to a conventional tablet preparation method.

Formulation Example 3: Preparation of Capsule

Juju Cheonin Guk Juice (EPJ) Powder 10 mg

3 mg of crystalline cellulose

14.8 mg lactose

Magnesium stearate 0.2 mg

According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare a capsule.

Formulation Example 4: Preparation of granules

Juju Cheonin Guk Juice (EPJ) Powder 1,000 mg

Vitamin mixture right amount

Vitamin A acetate 70 ㎍

1.0 mg of vitamin E

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

0.5 mg of vitamin B6

Vitamin B12 0.2 ㎍

Vitamin C 10 mg

Biotin 10 ㎍

1.7 mg of nicotinic acid amide

Folic acid 50 ㎍

0.5 mg of calcium pantothenate

Suitable amount of inorganic mixture

1.75 mg ferrous sulfate

Zinc oxide 0.82 mg

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Dicalcium phosphate 55 mg

90 mg of potassium citrate

100 mg of calcium carbonate

Magnesium chloride 24.8 mg

As for the composition ratio of the vitamin and mineral mixture, ingredients suitable for health functional foods are mixed in a preferred embodiment, but the mixing ratio may be arbitrarily modified, and the above ingredients are mixed according to a general health functional food manufacturing method. Next, granules are prepared and can be used to prepare a health functional food composition according to a conventional method.

Formulation Example 5: Preparation of beverage formulation

Juju Cheonin Guk Juice (EPJ) Powder 1,000 mg

1,000 mg citric acid

100 g oligosaccharides

2 g of plum concentrate

1 g taurine

Total 900 mL with purified water

After mixing the above ingredients according to a conventional beverage manufacturing method, after stirring and heating at 85° C. for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed and sterilized, and then stored in a refrigerator. It is used to prepare a functional beverage composition.

Formulation Example 6: Preparation of feed composition

JJU Cheonin Guk Juice (EPJ) powder 0.1 kg, corn 25.5 kg, wheat 15.04 kg, wheat flour 8.15 kg, rice bran 7.4 kg, soybean meal 18 kg, octane 1 kg, chicken by-products 14 kg, animal oil 9 kg, processed salt 0.3 kg , 0.3 kg of tricalcium phosphate, 1 kg of limestone, 0.01 kg of choline chloride, 0.05 kg of vitamins, 0.05 kg of minerals and 0.1 kg of digestive enzymes were mixed to prepare an animal (dog, dog) feed composition.

Claims (10)

1. A pharmaceutical composition for the treatment or prevention of allergic or inflammatory skin diseases, comprising the juice of Jajucheoninguk as an active ingredient.
2. The method of claim 1, wherein the allergic or inflammatory skin disease is skin inflammation, eczema, contact dermatitis, atopic dermatitis, seborrheic dermatitis, chronic lichen planus, interstitial dermatitis, deprived dermatitis, papular urticaria, psoriasis, psoriatic arthritis, sun dermatitis. , A pharmaceutical composition for treating or preventing allergic or inflammatory skin diseases, characterized in that any one skin disease selected from sunburn and acne.
3. The pharmaceutical composition for the treatment or prevention of allergic or inflammatory skin diseases according to claim 1, wherein the self-made Cheonin-guk is a stem, leaf, or above-ground outpost of self-made Cheonin-guk.
4. The pharmaceutical composition for treating or preventing allergic or inflammatory skin diseases according to claim 1, wherein the pharmaceutical composition is an oral preparation.
5. The pharmaceutical composition for the treatment or prevention of allergic or inflammatory skin diseases according to claim 4, wherein the oral preparation is a powder, granule, tablet, capsule, troche, suspension, emulsion, syrup or aerosol.
6. Animal pharmaceutical composition for the treatment or prevention of allergic or inflammatory skin diseases, comprising the juice of Jaju Cheonin Guk as an active ingredient.
7. A food composition for improving allergic or inflammatory skin diseases, including the juice of Jajucheoninguk as an active ingredient.
8. The food composition for improving allergic or inflammatory skin diseases according to claim 7, wherein the food composition is a powder, granule, tablet, capsule, pill, extract, jelly formulation, tea bag formulation, or beverage formulation.
9. The food composition according to claim 7, wherein the food composition is a health functional food for improving allergic or inflammatory skin diseases.
10. A feed composition for improving allergic or inflammatory skin diseases, comprising the juice of Jajucheonin-guk as an active ingredient.