WO2023204363A1 - Composition for preventing, ameliorating, or treating atopic dermatitis comprising extract of alpinia officinarum hance as active ingredient - Google Patents

Abstract

The present invention relates to a composition for preventing, ameliorating, or treating atopic dermatitis comprising an extract of Alpinia officinarum Hance as an active ingredient. Specifically, as an extract of Alpinia officinarum Hance suppresses an increase in ear thickness in an animal model with atopic dermatitis, ameliorates skin lesions such as skin damage and the like, and has an excellent effect in reducing the secretion of chemokine and immunoglobulin E, the extract of Alpinia officinarum Hance can be effectively used in functional health foods, pharmaceutical products, etc. for atopic dermatitis.

Description

Composition for preventing, improving or treating atopic dermatitis containing Goryangkang extract as an active ingredient

The present invention relates to a composition for preventing, improving, or treating atopic dermatitis containing an extract of Goryanggang as an active ingredient.

Recently, atopy is a type of hypersensitivity whose risk has been greatly highlighted as its prevalence has rapidly increased. From an immunological perspective, the main symptoms are caused by the immune reaction of immunoglobulin E and allergens. It is defined as a group of allergic diseases with a strong genetic tendency. In particular, atopic dermatitis, a representative symptom of atopy, has serious symptoms in 0.5 to 1% of the general population and 5 to 10% of children, but it is presumed to be related to genetic factors and immune system deficiency. The exact cause has not been revealed, and it is expected to be alleviated somewhat by improving the environment and diet, but there is no fundamental treatment method.

However, although there are individual differences in atopic dermatitis, most cases include extreme itching, dry skin, rashes, oozing, scabs, and scaly skin (scaly skin), resulting in emotional anxiety, stress, tension, and frustration. , along with feelings of anger, it is frequently accompanied by other allergic diseases such as hives, metal allergy, asthma, and allergic rhinitis, and is emerging as a serious social problem that threatens public health today. Meanwhile, representative drugs known to be effective for atopic dermatitis to date include steroids, antihistamines, antibiotics, non-steroids, and other sedatives and tranquilizers.

Meanwhile, Alpinia officinarum Hance is a perennial herb belonging to the ginger family. The rhizome is dug up in the fall and dried. In eastern medicine, it is said to be effective in treating abdominal pain, vomiting and diarrhea, as well as poor kidney function, loss of stamina due to sensitivity to cold, and dysentery. It is known that its main pharmacological actions include promoting gastric juice secretion, analgesic action, anti-oxidation effect, anti-thrombotic action, anti-coagulant action, and improvement of peripheral circulation.

As for prior art related to atopic dermatitis, Korean Patent No. 2282256 discloses ‘Composition for preventing, improving or treating atopic dermatitis containing extract of Siberia chinensis root’, and Korean Patent No. 1874462 discloses ‘Scisandra chinensis leaf extract as active ingredient. A composition for preventing, improving, or treating atopic dermatitis comprising a 'composition' is disclosed. However, the present invention's 'composition for preventing, improving or treating atopic dermatitis containing Goryanggang extract as an active ingredient' has not yet been disclosed.

The present invention was developed in response to the above-mentioned needs, and the present invention provides a composition for preventing, improving or treating atopic dermatitis containing the Koryang-gang extract as an active ingredient, and the Koryang-gang extract is used to treat the ear thickness of an atopic dermatitis animal model. The present invention was completed by confirming that it suppresses the increase, improves skin lesions such as skin damage, and reduces the secretion amount of chemokines (MDC and RANTES) and immunoglobulin E (IgE).

In order to solve the above problems, the present invention provides a health functional food composition for preventing or improving atopic dermatitis, containing an extract of Goryanggang as an active ingredient.

In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of atopic dermatitis containing an extract of Goryanggang as an active ingredient.

In addition, the present invention provides a quasi-drug for preventing or improving atopic dermatitis containing Goryangkang extract as an active ingredient.

In addition, the present invention provides a feed additive for preventing or improving atopic dermatitis containing Goryang River extract as an active ingredient.

The present invention relates to a composition for preventing, improving or treating atopic dermatitis containing Goryanggang extract as an active ingredient. Goryanggang extract inhibits the increase in ear thickness in an atopic dermatitis animal model and improves skin lesions such as skin damage. It has the effect of reducing the secretion of chemokines (MDC and RANTES) and immunoglobulin E (IgE).

Figure 1 is a schematic diagram of an animal test method that confirmed the improvement effect of atopic dermatitis by administering the Goryanggang extract of the present invention in an animal model in which atopic dermatitis was induced through DfE ( Dermatophagoides farinae extract) treatment.

Figure 2 shows the results of visual observation of the degree of skin damage in each experimental group following administration of the Goryang River extract (AOWex) of the present invention in an animal model in which atopic dermatitis was induced. DfE(-) is the normal group not treated with natural mite-derived extract ( Dermatophagoides farinae extract), DfE(+) is the atopic dermatitis group induced by treatment with natural mite-derived extract ( Dermatophagoides farinae extract), and AOWex is Goryanggang extract. The administration group, Dexa, is the dexamethasone administration group, which is the positive control group.

Figure 3 shows the results of confirming the ear thickness and skin damage degree (dermatitis score) of mice following administration of the Goryanggang extract (AOWex) of the present invention in an animal model in which atopic dermatitis was induced. Normal is the normal group, AD is the atopic dermatitis-induced group, AOWex is the Goryanggang extract administration group, and Dexa is the dexamethasone administration group, which is a positive control group. #### indicates a statistically significant increase in the ear thickness and degree of skin damage in the atopic dermatitis induced group compared to the normal group, p<0.0001. **** indicates a statistically significant decrease in the ear thickness and degree of skin damage in the high-lyanggang administration group (AOWex) and the positive control group, the dexamethasone administration group, compared to the atopic dermatitis induction group, p<0.0001.

Figure 4 shows the results of confirming the contents of MDC, RANTES, and IgE in serum according to administration of the Goryang River extract (AOWex) of the present invention in an animal model in which atopic dermatitis was induced. DfE(-) is the normal group not treated with natural mite-derived extract ( Dermatophagoides farinae extract), DfE(+) is the atopic dermatitis group induced by treatment with natural mite-derived extract ( Dermatophagoides farinae extract), and AOWex is Goryang River. This is the extract administration group, and Dexa is the dexamethasone administration group, which is the positive control group. #### indicates a statistically significant increase in the content of MDC, RANTES, and IgE in the serum of the atopic dermatitis group compared to the normal group, p<0.0001. *, **, **** indicate a statistically significant decrease in the content of MDC, RANTES and IgE in the serum of the group administered the Goryanggang extract of the present invention and the dexamethasone administered group as a positive control group compared to the atopic dermatitis group, * represents p <0.05, ** is p<0.01, and **** is p<0.0001.

In order to achieve the object of the present invention, the present invention provides a health functional food composition for preventing or improving atopic dermatitis, comprising an extract of Goryanggang as an active ingredient.

The Goryang River extract can be prepared by a method including the following steps, but is not limited to this:

(1) Extracting by adding an extraction solvent to Goryang River;

(2) filtering the extract of step (1); and

(3) Concentrating and drying the filtered extract of step (2) to prepare an extract.

In step (1), the extraction solvent is preferably selected from water, lower alcohols of C ₁ to C ₄ , or mixtures thereof, more preferably water, but is not limited thereto.

In the above manufacturing method, the extraction method can be any conventional method known in the art, such as filtration, hot water extraction, immersion extraction, reflux cooling extraction, and ultrasonic extraction. The extraction solvent is preferably added at 1 to 20 times the weight of Goryang River for extraction, and more preferably at 5 to 15 times. The extraction time is preferably 0.5 to 10 hours, more preferably 0.5 to 5 hours, but is not limited to this. In the above method, the vacuum concentration in step (3) is preferably performed using a vacuum vacuum concentrator or a vacuum rotary evaporator, but is not limited thereto. In addition, drying is preferably performed by reduced pressure drying, vacuum drying, boiling drying, spray drying, or freeze drying, but is not limited thereto.

The composition is preferably manufactured in a dosage form selected from powder, granule, pill, tablet, capsule, candy, syrup and beverage, but is not limited thereto.

When using the health functional food composition of the present invention as a food additive, the Koryanggang extract can be added as is or used together with other foods or food ingredients, and can be used appropriately according to conventional methods. The mixing amount of the active ingredient can be appropriately determined depending on the purpose of use (prevention or improvement). Generally, when producing a food or beverage, the composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on the raw materials. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.

There are no special restrictions on the types of foods above. Examples of foods to which the extract can be added include meat, sausages, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, These include alcoholic beverages and vitamin complexes, and include all health functional foods in the conventional sense.

When the composition of the present invention is used as a health drink, it may contain various flavoring agents or natural carbohydrates as additional ingredients like conventional drinks. The above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as textrin and cyclotenstrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As a sweetener, natural sweeteners such as thaumarin and stevia extract or synthetic sweeteners such as saccharin or aspartame can be used. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g, per 100 g of the composition of the present invention. The composition of the present invention contains various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal neutralizer, pH adjuster, stabilizer, preservative, glycerin, alcohol, carbonic acid. It may contain carbonating agents used in beverages. Additionally, the composition of the present invention may contain pulp for the production of natural fruit juice, fruit juice beverages, and vegetable beverages. These ingredients can be used independently or in combination. The ratio of these additives is not very important, but the composition of the present invention is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight.

In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of atopic dermatitis containing an extract of Goryanggang as an active ingredient.

The composition of the present invention may further include pharmaceutically acceptable carriers, excipients, or diluents in addition to the above active ingredients, and may be in various oral or parenteral dosage forms. When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include capsules, powders, granules, tablets, pills, etc. These solid preparations contain one or more compounds and at least one excipient, such as starch, calcium carbonate, sucrose, or lactose ( It is prepared by mixing lactose, gelatin, etc. Additionally, in addition to simple excipients, lubricants such as magnesium stearate, talc, etc. are also used. Liquid preparations for oral administration include suspensions, emulsions, syrups, aerosols, etc. In addition to the commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. . Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspension solvents may include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. As a base for suppositories, witepsol, macrogol, tween 61, cacao, laurel, glycero gelatin, etc. can be used. When administering parenterally, it is preferable to choose external dermal application or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine dura, or intracerebrovascular injection.

The pharmaceutical composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat the disease with a reasonable benefit/risk ratio applicable to medical treatment, and the level of the effective amount is determined by the type, severity, and activity of the patient's disease. , can be determined based on factors including sensitivity to the drug, time of administration, route of administration and excretion rate, duration of treatment, concurrently used drugs, and other factors well known in the medical field. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or multiple times. Considering all of the above factors, it is important to administer an amount that can achieve maximum effect with the minimum amount without side effects, and this can be easily determined by a person skilled in the art.

The dosage of the composition of the present invention varies depending on the patient's weight, age, gender, health condition, diet, administration time, administration method, excretion rate, and severity of disease. The composition of the present invention can be used alone or in combination with surgery, radiation therapy, hormone therapy, chemotherapy, and methods using biological response modifiers.

In addition, the present invention provides a quasi-drug for preventing or improving atopic dermatitis containing Goryangkang extract as an active ingredient.

The term "quasi-drug" used in the present invention refers to products with a milder effect than pharmaceuticals among products used for the purpose of diagnosing, treating, improving, alleviating, treating or preventing diseases in humans or animals. For example, according to the Pharmaceutical Affairs Act. According to it, quasi-drugs exclude products used for medicinal purposes, and include products used to treat or prevent diseases in humans and animals, or products that have a mild or no direct effect on the human body.

The quasi-drug of the present invention is used for the purpose of improving atopic dermatitis, and there is no particular limitation in its formulation. In each formulation, the quasi-drug can arbitrarily select and mix other ingredients depending on the formulation or purpose of use of the other quasi-drug. there is. The amount of active ingredients mixed can be appropriately determined depending on the purpose of use (suppression or alleviation). For example, it may include conventional auxiliaries such as thickeners, stabilizers, solubilizers, vitamins, pigments and flavors, and carriers.

In addition, the present invention provides a feed additive for preventing or improving atopic dermatitis containing Goryang River extract as an active ingredient.

The feed additive of the present invention corresponds to supplementary feed under the Feed Management Act. In the present invention, the term 'feed' may mean any natural or artificial diet, meal, etc., or a component of the meal, for or suitable for eating, ingestion, and digestion by animals. The type of feed is not particularly limited, and feed commonly used in the art can be used. Non-limiting examples of the feed include plant feeds such as grains, roots and fruits, food processing by-products, algae, fiber, pharmaceutical by-products, oils and fats, starches, cucurbits or grain by-products; Examples include animal feeds such as proteins, inorganic substances, fats and oils, minerals, oils and fats, single-cell proteins, zooplanktons or food. These may be used alone or in combination of two or more types.

Hereinafter, the present invention will be described in detail through examples. However, the following examples only illustrate the present invention, and the content of the present invention is not limited to the following examples.

Materials and Methods

1. Experimental animals

Five-week-old male NC/Nga mice were supplied by JoongAng Laboratory Animal Co., Ltd. Animals were housed in mouse cages (220 mm), 5 animals were reared. Purina Rat Chow, a pellet-type solid feed for laboratory animals, was supplied and fed from Nestle Purina PetCare Korea Ltd. (Seoul, Korea), and sterilized purified water was autonomously drunk using an automatic water supply device. They were used in experiments after being adapted to the breeding environment for 7 days.

2. Establishment of atopic dermatitis model and sample administration

150㎕ of 4% Sodium Dodecyl Sulfate (SDS) was applied to the shaved back skin and ear surface of NC/Nga mice after an acclimatization period for one week to destroy the skin barrier and induce allergic atopy 3 hours later. 100 mg of ointment (Biostir Inc.) containing an antigen derived from natural house dust mites (DfE, Dermatophagoides farina extract) was applied. Mice were applied DfE ointment twice a week for a total of 3 weeks. Seven days after the initial application of DfE ointment, Goryanggang extract (AOWex) or dexamethasone (Dexa; positive control) dissolved in sterilized purified water was orally administered daily for 14 days (Figure 1). NC/Nga mice were randomly divided into five groups: normal group (untreated with DfE), atopic dermatitis-induced group (treated with DfE), AOWex administered group (30, 100, 300 mg/kg of Goryanggang extract), and Dexa administered group (dexamethasone). Classified.

3. Measurement of ear thickness and dermatitis score

Ear thickness was measured twice a week using a digital caliper purchased from CAS Chemicals. The degree of skin damage was indicated based on four symptoms: swelling of the dorsal skin and ear lesions, scarring/dryness, erythema/bleeding, and rash/fever. Individual scores were assigned to 0 (no symptoms), 1 (mild), 2 (moderate), or 3 (severe) for each symptom category, and the degree of skin damage was defined as the sum of the individual scores.

4. Serum analysis

On the 23rd day of the experiment, mouse blood samples obtained through cardiac blood collection were reacted at room temperature for 30 minutes and then centrifuged (13000 rpm, 15 min) to obtain serum. The total concentration of immunoglobulin E (IgE) in serum was measured using the LBIS mouse IgE ELISA kit purchased from Fujifilm, and the serum levels of total MDC and RANTES were measured using an ELISA kit purchased from R&D Systems. It was measured. All serum measurement experiments were analyzed according to the protocol provided by the manufacturer.

5. Statistical processing

All data were analyzed using the GraphPad Prism version 8.0 program. Data were expressed as mean ± standard error (SEM) and calculated using analysis of variance. One-way ANOVA was performed for comparison between each group, and the significance between each group was verified using Duncan's multiple comparison test as a post hoc test. If the p value was less than 0.05, it was determined that there was a statistically significant difference.

Example 1. Preparation of Goryang River extract

Add 1 kg of dried Alpinia officinarum to 10 liters of distilled water, reflux and extract at 100 ± 2°C for 3 hours, filter through a strainer, and perform secondary filtration using a test sieve (Test Sieve 53㎛ No. 270). The Goryang River extract was obtained, and it was freeze-dried.

In animal experiments, the freeze-dried extract was dissolved in sterilized purified water and used. In the cell experiment, Goryang River thermal water extract dissolved in distilled water was filtered through a 0.22㎕ filter and then used in the experiment.

Example 2. Confirmation of the degree of skin damage following administration of Goryanggang extract in an animal model with induced atopic dermatitis

The ear thickness and skin damage (dermatitis score) of mice following administration of the Goryanggang extract of the present invention were confirmed.

As a result, in the atopic dermatitis induced group (DfE treated) compared to the normal group (DfE untreated), skin dryness to severe scarring, erythema, bleeding, abrasions and erosions were observed, and in contrast, the administration of the Goryanggang extract of the present invention showed It was confirmed that damaged skin symptoms were improved in a concentration-dependent manner (Figure 2).

In addition, as shown in Figure 3, the ear thickness and degree of skin damage were statistically significantly increased in the atopic dermatitis-induced group (AD) compared to the normal group, and in contrast, after the 7th day, the high dose administration group of all concentrations In (AOWex), there was a statistically significant decrease in ear thickness and degree of skin damage.

Example 3. Confirmation of MDC, RANTES, and IgE contents in serum according to administration of Goryanggang extract in an animal model with induced atopic dermatitis

The contents of MDC, RANTES, and IgE in the serum of mice following administration of the Goryanggang extract of the present invention were confirmed.

As a result, as shown in Figure 4, the contents of MDC, RANTES and IgE were statistically significantly increased in the atopic dermatitis induced group (DfE treated) compared to the normal group (DfE untreated), and compared to the atopic dermatitis induced group, the In the Goryang River extract treatment group (AOWex), the contents of MDC, RANTES, and IgE were statistically significantly decreased.

Claims (7)

A health functional food composition for preventing or improving atopic dermatitis containing Goryang River extract as an active ingredient. The health functional food composition for preventing or improving atopic dermatitis according to claim 1, wherein the extraction solvent of the Goryanggang extract is water, C ₁ to C ₄ lower alcohol, or a mixture thereof. The health functional food composition for preventing or improving atopic dermatitis according to claim 1, wherein the composition is manufactured in a formulation selected from powder, granule, pill, tablet, capsule, candy, syrup, and beverage. A pharmaceutical composition for preventing or treating atopic dermatitis, comprising an extract of Goryang River as an active ingredient. The pharmaceutical composition for preventing or treating atopic dermatitis according to claim 4, further comprising a pharmaceutically acceptable carrier, excipient, or diluent in addition to the active ingredient. A quasi-drug for preventing or improving atopic dermatitis containing Goryang River extract as an active ingredient. A feed additive for preventing or improving atopic dermatitis containing Goryang River extract as an active ingredient.

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