KR20230039887A - Composition for preventing or treating inflammatory raspiratory diseases caused by ultrafine dust containing mugwort and lizard’s tail extract as an active ingredient - Google Patents

Abstract

The present invention relates to a composition for preventing or treating inflammatory respiratory diseases caused by fine dust, containing a mixed extract of Artemisia princeps and Saururus chinensis. The mixed extract of Artemisia princeps and Saururus chinensis of the present invention has an excellent effect of preventing, alleviating, and treating inflammatory respiratory diseases caused by ultrafine dust. Therefore, the present invention can be used as a pharmaceutical composition for preventing or treating respiratory diseases caused by ultrafine dust, a health functional food composition for preventing or alleviating respiratory diseases caused by ultrafine dust, or a cosmetic composition for preventing or alleviating skin inflammation caused by ultrafine dust.

Description

Composition for preventing or treating inflammatory respiratory diseases caused by ultrafine dust containing mugwort and lizard's tail extract as an active ingredient}

The present invention relates to a composition for preventing or treating inflammatory respiratory diseases caused by fine dust, including a mixed extract of mugwort and Sambakcho.

Air pollution is highly correlated with non-communicable diseases such as respiratory diseases, cardiovascular and metabolic abnormalities, cognitive impairment and childhood developmental disorders. As the industry has advanced due to the development of science and technology, life has expanded quantitatively and become more convenient. According to World Health Organization (WHO) data released in 2018, as of 2016, more than 91% of the world's population lives in areas that do not meet the WHO air quality guidelines level, and air pollution There are 4.2 million premature deaths per year. Air pollution exposure is reported to have a higher risk of disease than commonly known controllable disease risk factors such as lack of exercise, high salt diet, hyperlipidemia, and drug misuse.

Particulate matter (PM) is not a single substance, but a complex mixture consisting of fine solid and liquid particles of organic and inorganic components suspended in the air. As the fact that the smaller the particle size is, the more harmful to health, fine dust is subdivided into PM ₁₀ (when the particle diameter is smaller than 10 μm) and PM _2.5 (when the particle diameter is smaller than 2.5 μm), and fine dust and referred to as fine dust.

Today, fine dust is attracting a lot of attention as a hazard to health. Dust of 5-10 μg/ ^m3 or less can be absorbed into the body through the nasal mucosa, dust of 2-5 μg/m3 or less passes through the airways, and dust as small as 0.1-1 μg/ ^m3 damages the alveoli. can induce up to According to the World Health Organization (WHO), long-term exposure to PM ₁₀ increases respiratory health and mortality, and PM _2.5 acts as a stronger risk factor. Every 10 μg/ ^m3 increase in atmospheric PM ₁₀ increases daily mortality by 0.2–0.6%, and a 10 μg/ ^m3 average increase in long-term exposure to PM _2.5 increases mortality from cardiovascular disease by 6–13 increase by approx. In October 2013, the International Agency for Research on Cancer (IARC) under the World Health Organization classified fine dust as a group 1 carcinogen.

Dust with a diameter of 5 to 10 μg/m ³ or less can be absorbed into the body through the nasal mucosa, 2 to 5 μg/m ³ or less passes through the airway (respiratory tract), and 0.1 to 1 μg/m ³ to alveolar damage. it causes When fine dust is inhaled into the human body, it can be deposited in tissues by various mechanisms such as collision, gravitational sedimentation, diffusion, and electrostatic adsorption, and some circulate throughout the body along the blood. In addition, studies on fine dust and the central nervous system are mainly about cerebrovascular disease. The vascular inflammatory mechanism in which fine dust contributes to cardiovascular disease occurs similarly in cerebrovascular, thereby increasing the risk of cerebrovascular disease. It has been found that by amplifying the response, it causes damage to brain cells and causes neurological diseases such as Alzheimer's and dementia.

On the other hand, mugwort is traditionally a food familiar to Koreans and has a long history of being used for medicinal purposes. In folk remedies, the warm nature of mugwort has been used to treat sedatives, convulsions, paralysis, and stiffness of the body. , It is said that mugwort was used to treat abdominal pain, hematemesis, jaundice, anorexia, and hemostasis (Heo Jun, 2005; Jeong Bo-seop, 1990; Traditional Medicine Research Institute, 1994; Yoo Tae-jong, 1999). According to recent reports, mugwort is rich in antioxidants such as total phenols and flavonoids, which inhibit oxidative damage (Lee et al., 2011; Lee et al., 1992; Hong et al., 2007) and have anticancer effects (Jung et al., 2008; Kim et al., 2012; Kim et al., 2005), anti-ulcer and anti-inflammatory action (Jang, 1993; Kwon et al., 2011; Min et al., 2009), anti-diabetes (Kang et al., 2008; Al-Mustafa and Al-Thunib, 2008; Kang, 2008), It is said to have a great effect on antibacterial activity (Lee et al., 1999; Lee and Seo, 2003), immunity enhancement (Lee, 2013), and is also known to be effective in circulatory diseases such as blood pressure and cardiovascular system.

On the other hand, lizard's tail is a perennial herb belonging to the genus Saururus in the family Saururaceae, and its scientific name is Saururus cernuus . As a herb that has been traditionally used as a medicinal plant in Korea and China, it is described in the Chinese Medicine Dictionary that Sambaekcho has a detoxifying effect on moist heat and small species, and is effective for species, beriberi, jaundice, jaundice, clams, carbuncles, and poisoning. Studies on the effects on inflammation, beriberi, hypertension, pneumonia, edema, jaundice, gonorrhea, etc. have been reported (Oh, KS et al, Planta Med. 74:233-238, 2008; Korean Registered Patent No. 0739398; International Patent WO 2008/082268 A1; Republic of Korea Patent Publication No. 2006-0018290).

The inventors of the present invention completed the present invention by confirming that the mixed extract of mugwort and sambaekcho reduces oxidative stress, improves mitochondrial dysfunction due to ultrafine dust toxicity, and suppresses inflammatory reactions.

An object of the present invention is to provide a pharmaceutical composition for preventing or treating inflammatory respiratory diseases caused by ultrafine dust containing a mixed extract of mugwort and sagebrush.

In addition, another object of the present invention is to provide a health functional food composition for preventing or improving inflammatory respiratory diseases caused by ultrafine dust, including a mixed extract of mugwort and sagebrush.

In addition, another object of the present invention is to provide a health food composition for preventing or improving inflammatory respiratory diseases caused by ultrafine dust containing a mixed extract of mugwort and sagebrush.

Lastly, another object of the present invention is to provide a cosmetic composition for preventing or improving skin inflammation caused by ultrafine dust containing a mixed extract of mugwort and sagebrush.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating inflammatory respiratory diseases caused by ultrafine dust, including a mixed extract of mugwort and 3 baekcho.

Next, the present invention provides a health functional food composition for preventing or improving inflammatory respiratory diseases caused by ultrafine dust, including a mixed extract of mugwort and sagebrush.

Furthermore, the present invention is to provide a health food composition for preventing or improving inflammatory respiratory diseases caused by ultrafine dust containing a mixed extract of mugwort and sagebrush.

In addition, the present invention provides a cosmetic composition for preventing or improving skin inflammation caused by ultrafine dust containing a mixed extract of mugwort and sagebrush.

The mixed extracts of mugwort and sagebrush of the present invention are excellent in preventing, improving, and treating inflammatory respiratory diseases caused by ultrafine dust, so that a pharmaceutical composition for preventing or treating respiratory diseases caused by ultrafine dust, It can be used as a health functional food composition for preventing or improving respiratory diseases or a cosmetic composition for preventing or improving skin inflammation caused by ultrafine dust.

1 is a graph showing the results of evaluating the cytotoxicity of a single extract of mugwort or sambaekcho.
Figure 2 is a graph showing the results of cytotoxicity evaluation of the mixed extract of mugwort and sambaekcho.
Figure 3 is a graph showing the results of LC / MS-MS analysis of the mixed extract of mugwort and sambaekcho.
Figure 4 is a diagram showing the results of analysis of the expression of inflammation-related proteins in the mixed extracts of mugwort and 300 seconds in lung tissue and olfactory bulb tissue.

Hereinafter, the present invention will be described in detail as an embodiment of the present invention with reference to the accompanying drawings. However, the following implementation examples are presented as examples of the present invention, and if it is determined that a detailed description of a well-known technology or configuration may unnecessarily obscure the gist of the present invention, the detailed description may be omitted. , the present invention is not limited thereby. Various modifications and applications of the present invention are possible within the description of the claims described later and equivalent scopes interpreted therefrom.

In addition, terms used in this specification (terminology) are terms used to appropriately express preferred embodiments of the present invention, which may vary according to the intention of a user or operator or customs in the field to which the present invention belongs. Therefore, definitions of these terms should be made based on the contents throughout this specification. Throughout the specification, when a certain component is said to "include", it means that it may further include other components without excluding other components unless otherwise stated.

Throughout this specification, '%' used to indicate the concentration of a particular substance is solid/solid (w/w) %, solid/liquid (w/v) %, and Liquid/liquid is (v/v) %.

The present invention provides a pharmaceutical composition for preventing or treating inflammatory respiratory diseases caused by ultrafine dust comprising a mixed extract of mugwort and sagebrush.

The term "mugwort" used in the present invention refers to mugwort, a perennial herbaceous plant belonging to the Asteraceae family with strong fertility, and there are about 2,000 species, and about 300 species are known in Korea. It has been used for digestion, lower abdominal pain, anthelmintic, and odor removal. In addition, it is reported to be effective in lung diseases, asthma, fatigue recovery, etc. because it is rich in essential oil components such as cineol, vitamins, and minerals.

In addition, the mugwort includes mugwort ( Artemisia princeps ), dog wormwood ( Artemisia annua ), injin mugwort ( Artemisia capillaris ), true mugwort ( Artemisia dubia ), yellow sea mugwort ( Artemisia argyi ), etc., preferably Yellow Sea mugwort ( Artemisia argyi ) It may be, but any plant belonging to the genus Artemisia may be included without limitation.

The term "lizard's tail" used in the present invention refers to Saururus chinensis of the order of pepper 300 and has been used as a herbal medicine in oriental medicine. It is known that the taste is bitter and spicy, the flowers and roots are white, and 2 to 3 leaves on the upper part turn white when the flowers bloom, and the fruits run round one by one on the bud around September to October.

The extract according to the present invention may be obtained by extraction and separation from nature using extraction and separation methods known in the art, and the "extract" defined in the present invention refers to mugwort ( Artemisia argyi ) using an appropriate solvent. And it is extracted from Saururus chinensis , and includes, for example, a crude extract, a polar solvent-soluble extract, or a non-polar solvent-soluble extract. The mugwort ( Artemisia argyi ) and Saururus chinensis ( Saururus chinensis ) As a suitable solvent for extracting the extract, any organic solvent acceptable in food science / pharmacy / cosmetics may be used, and water or an organic solvent may be used, Although not limited thereto, for example, purified water, alcohol having 1 to 4 carbon atoms including methanol, ethanol, propanol, isopropanol, butanol, etc., acetone ), ether, benzene, chloroform, ethyl acetate, methylene chloride, hexane and cyclohexane, etc. alone or mixed and can be used. As an extraction method, any one of methods such as hot water extraction, cold brew extraction, reflux cooling extraction, solvent extraction, steam distillation, ultrasonic extraction, elution, and compression may be selected and used. In addition, the desired extract may be additionally subjected to a conventional fractionation process or may be purified using a conventional purification method.

There is no limitation on the preparation method of the extract of the present invention, and any known method may be used. For example, the extract included in the composition of the present invention can be prepared in a powder state by additional processes such as distillation under reduced pressure and freeze drying or spray drying of the primary extract extracted by the above-described hot water extraction or solvent extraction method. In addition, a fraction further purified from the primary extract using various chromatography such as silica gel column chromatography, thin layer chromatography, and high performance liquid chromatography you can also get Therefore, in the present invention, the extract is a concept that includes all extracts, fractions, and purified products obtained in each step of extraction, fractionation, or purification, and dilutions, concentrates, or dried products thereof.

In addition, the mixed extract may be a mixture of mugwort and sambaekcho in a weight ratio of 6: 4, but is not limited thereto.

In addition, the respiratory disease is an inflammatory respiratory disease consisting of pneumonia, asthma, chronic bronchitis, pneumoconiosis, tuberculosis, emphysema, chronic obstructive pulmonary disease, cystic fibrosis, cough, sputum, sore throat, tonsillitis, sinusitis, rhinitis, obstructive bronchiolitis and laryngitis It may be selected from the group, but is not limited thereto.

In addition, the mixed extracts of mugwort and sambaekcho may inhibit malondialdehyde and increase superoxide dismutase and reduced glutathione, but are not limited thereto.

In addition, the mixed extract of mugwort and sambaekcho may improve mitochondrial dysfunction caused by ultrafine dust, but is not limited thereto.

In addition, the mixed extract of mugwort and Sambakcho may inhibit the increase of p-JNK, p-IκB-α, p-NF-κB, TNF-α, IL-1β and COX-2 caused by ultrafine dust, It is not limited thereto.

In the present invention, the term "prevention" refers to any action that suppresses or delays the occurrence, development, and recurrence of inflammatory respiratory diseases caused by ultrafine dust by administration of the composition according to the present invention.

As used herein, the term "treatment" means any action that improves or beneficially changes the symptoms of inflammatory respiratory diseases caused by ultrafine dust and complications caused by the administration of the composition according to the present invention. Those of ordinary skill in the art to which the present invention pertains will be able to determine the degree of improvement, enhancement and treatment by knowing the exact criteria of the disease for which the composition of the present application is effective by referring to the data presented by the Korean Medical Association, etc. will be.

The composition according to the present invention may include a pharmaceutically effective amount of a mixed extract of mugwort and triticale, or may include one or more pharmaceutically acceptable carriers, excipients, or diluents. In the above, the pharmaceutically effective amount refers to an amount sufficient to prevent, improve, and treat symptoms of immune diseases. In the above, "pharmaceutically acceptable" refers to a composition that is physiologically acceptable and does not cause allergic reactions such as gastrointestinal disorders and dizziness or similar reactions when administered to humans.

In addition, the composition of the present invention can be administered orally or parenterally during clinical administration and can be used in the form of general pharmaceutical preparations. Dosage forms may be oral, mucosal (eg nasal, sublingual, vaginal, buccal, or rectal), parenteral (eg subcutaneous, intravenous, bolus infusion, intramuscular or intraarterial), topical (eg subcutaneous, intravenous, bolus infusion, intramuscular or intraarterial). , eye), transdermal or transcutaneous method, but is not limited thereto. Examples of dosage forms include tablets; caplets; capsule agents such as soft elastic gelatin capsules; cachets; Troki; lozenges; dispersant; suppositories; powder; aerosols (eg, nasal sprays or inhalers); gel; liquid dosage forms suitable for oral or mucosal administration to patients, including suspension preparations (eg, aqueous or non-aqueous liquid suspension preparations, oil-in-water emulsions, or water-in-oil liquid emulsions) solutions and elixirs; liquid dosage forms suitable for injectable administration to patients; eye drops or other ophthalmic preparations suitable for topical administration; and sterile solid preparations (eg, crystalline or amorphous solids) that can be reconstituted to provide a liquid dosage form suitable for injectable administration to a patient. The types, shapes, and types of dosage forms of the present invention generally vary widely depending on their use. For example, a dosage form used for acute treatment of a condition may contain a higher amount of the active ingredient than a dosage form used for chronic treatment of the same condition. Also, a parenteral dosage form may contain a smaller amount of the active ingredient than an oral dosage form used to treat the same condition. A wide variety of dosage forms and modes encompassed by the present invention are readily apparent to those skilled in the art to which this invention pertains (see Remington's Pharmaceutical Sciences, 18th ed., Mack Publishing, Easton PA (1990)). .)

In addition, the composition including a pharmaceutically acceptable carrier may be in various oral or parenteral formulations. When formulated, it may be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. The carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, It may be at least one selected from the group consisting of polyvinyl pyrrolidone, physiological saline, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil, dextrin, calcium carbonate, propylene glycol, and liquid paraffin. It is not limited, and all conventional carriers, excipients or diluents can be used. The above ingredients may be added independently or in combination with the active ingredients, the mixed extract of mugwort and sambaekcho.

The pharmaceutical composition of the present invention may be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically applied) according to the desired method, and the dosage is determined according to the patient's body weight, age, sex, The range varies according to health status, diet, administration time, administration method, excretion rate, and severity of disease.

In addition, solid preparations for oral administration may include tablets, pills, powders, granules, capsules, etc., and such solid preparations may contain at least one excipient, for example, starch, calcium carbonate, sucrose, etc., in one or more compounds. Alternatively, it may be prepared by mixing lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral administration include suspensions, internal solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. there is.

In addition, formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspension solutions, emulsions, freeze-dried formulations, suppositories, and the like. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerol, gelatin, and the like may be used.

In addition, the pharmaceutical composition of the present invention can be used parenterally in the form of an injection of a sterile solution or suspension in water or other pharmaceutically acceptable liquids, if necessary. For example, in appropriate combination with a pharmacologically acceptable carrier or medium, specifically, sterile water or physiological saline, vegetable oil, emulsifier, suspending agent, surfactant, stabilizer, excipient, vehicle, preservative, binder, etc., generally It is conceivable to formulate by blending into a unit dosage form required for recognized pharmaceutical practice. The amount of the active ingredient in the formulation is such that an appropriate dose within the indicated range can be obtained.

In addition, a sterile composition for injection can be prescribed according to conventional formulation practice using a vehicle such as distilled water for injection.

In addition, examples of aqueous solutions for injection include physiological saline, isotonic solutions containing glucose and other adjuvants, such as D-sorbitol, D-mannose, D-mannitol and sodium chloride; For example, alcohols, specifically ethanol, polyalcohols such as propylene glycol and polyethylene glycol, and nonionic surfactants such as polysorbate 80 (TM) and HCO-50 can be used in combination.

In addition, sesame oil and soybean oil can be cited as the oily liquid, and it can be used in combination with benzyl benzoate and benzyl alcohol as a solubilizing agent. It can also be combined with buffers such as phosphate buffer, sodium acetate buffer, analgesics such as procaine hydrochloride, stabilizers such as benzyl alcohol, phenol, antioxidants. The prepared injection solution is usually filled into an appropriate ampoule.

In addition, administration of the pharmaceutical composition of the present invention to the body of a patient is preferably parenteral administration, and specifically intrathecal intrathecal administration once to three times is basic, but further administration may be used. In addition, the administration time may be a short period of time or a long period of continuous administration. More specifically, injection form, transdermal administration form, etc. are mentioned. Examples of the injection formulation include intrathecal injection, intravenous injection, intraarterial injection, selective intraarterial injection, intramuscular injection, intraperitoneal injection, subcutaneous injection, intraventricular injection, intracerebral injection, intramedullary injection, etc. can do.

In addition, the pharmaceutical composition of the present invention is a group consisting of tablets, pills, powders, granules, capsules, suspensions, internal solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations and suppositories. It may have any one formulation selected from. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerol, gelatin, and the like may be used.

In addition, the effective dose for the human body of the mixed extract of mugwort and sambaekcho of the present invention may vary depending on the patient's age, weight, sex, dosage form, health condition, and degree of disease.

The pharmaceutical composition of the present invention can be used alone or in combination with methods using surgery, hormone therapy, drug therapy, and biological response modifiers for the prevention or treatment of inflammatory respiratory diseases caused by ultrafine dust.

Subsequently, the present invention provides a health functional food composition or health food composition for preventing or improving inflammatory respiratory diseases caused by ultrafine dust, including a mixed extract of mugwort and sambaekcho.

Since the health functional food or health food composition of the present invention includes the above-described mugwort and triticale mixed extract, the overlapping content with the aforementioned mugwort and triticale mixed extract of the present invention is excessive complexity of the present specification due to the overlapping description. The description is omitted to avoid

The food composition of the present invention can be formulated into various forms such as tablets, pills, granules, capsules, liquid preparations, and beverages and added to food. There is no particular restriction on the type of food. Examples of foods to which the mixed extract of mugwort and triticale of the present invention can be added include drinks, meat, sausages, bread, biscuits, rice cakes, chocolates, candies, snacks, confectionery, pizza, ramen, other noodles, gums, ice creams, including Dairy products, various soups, beverages, alcoholic beverages and vitamin complexes, dairy products and milk-processed products, etc., include both health foods and health functional foods in a conventional sense.

The health food and health functional food composition containing the mixed extract of mugwort and triticale according to the present invention may be added to food as it is or used together with other foods or food ingredients, and may be appropriately used according to conventional methods. The mixing amount of the mixed extract of mugwort and sambaekcho may be appropriately determined according to the purpose of use (for prevention or improvement). In general, the amount of the composition in health food and health functional food may be added in an amount of 0.1 to 90 parts by weight based on the total weight of food. However, in the case of long-term intake for the purpose of health maintenance or health control, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount greater than the above range.

The health food and health functional food composition of the present invention is not particularly limited in other components except for containing the mixed extract of mugwort and triticale of the present invention as essential components in the indicated ratio, and, like conventional beverages, various flavoring agents or natural carbohydrates, etc. may be included as an additional component. Examples of the aforementioned natural carbohydrates include monosaccharides such as glucose, fructose, and the like; disaccharides such as maltose, sucrose and the like; and polysaccharides such as conventional sugars such as dextrins, cyclodextrins, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (thaumatin, stevia extract (eg rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can advantageously be used. The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 of the health functional food composition of the present invention.

In addition to the above, the health food and health functional food composition containing the mixed extracts of mugwort and triticale of the present invention are various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants, and enhancers (cheese , chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, and the like. In addition, the health food and health functional food composition of the present invention may contain fruit flesh for preparing natural fruit juice, fruit juice beverages, and vegetable beverages.

These components may be used independently or in combination. The ratio of these additives is not so important, but it is generally selected in the range of 0.1 to about 20 parts by weight per 100 parts by weight of the health food and health functional food composition containing the mixed extract of mugwort and Sambakcho of the present invention.

In addition, the present invention provides a cosmetic composition for preventing or improving skin inflammation caused by ultrafine dust containing a mixed extract of mugwort and sagebrush.

Since the cosmetic composition of the present invention includes the above-mentioned mugwort and triticale mixed extract, the overlapping contents with the above-described mugwort and triticale mixed extract of the present invention are described in order to avoid excessive complexity of the present specification due to the overlapping description. omit

The "cosmetic composition" of the present invention is the above-described mugwort and It can be prepared by including a cosmetically effective amount of an extract extracted from Sambaekcho and a cosmetically acceptable carrier.

In the present specification, "cosmetically effective amount" means an amount sufficient to achieve the skin regeneration effect through the proliferation of epidermal keratinocytes of the composition of the present invention described above.

The appearance of the cosmetic composition contains a cosmetic or dermatologically acceptable medium or base. These are all formulations suitable for topical application, e.g. solutions, gels, solids, anhydrous pasty products, emulsions obtained by dispersing an oily phase in an aqueous phase, suspensions, microemulsions, microcapsules, microgranules or ionic forms (liposomes) and It may be provided in the form of a non-ionic follicular dispersant, or in the form of a cream, toner, lotion, powder, ointment, spray or conceal stick. These compositions can be prepared according to conventional methods in the art. The composition according to the present invention can also be used in the form of a foam or in the form of an aerosol composition further containing a compressed propellant.

The cosmetic composition according to an embodiment of the present invention is not particularly limited in its dosage form, for example, softening lotion, astringent lotion, nutrient lotion, nutrient cream, massage cream, essence, eye cream, eye essence, cleansing It can be formulated into cosmetics such as cream, cleansing foam, cleansing water, pack, powder, body lotion, body cream, body oil and body essence.

When the formulation of the cosmetic composition of the present invention is a paste, cream or gel, animal fibers, vegetable fibers, wax, paraffin, starch, tracanth, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide, etc. this can be used

When the formulation of the cosmetic composition of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and in particular, in the case of a spray, additionally chlorofluorohydro propellants such as carbon, propane/butane or dimethyl ether.

When the formulation of the cosmetic composition of the present invention is a solution or emulsion, a solvent, solvating agent or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene fatty acid esters of glycol, 1,3-butylglycol oil, glycerol aliphatic esters, polyethylene glycol or sorbitan.

When the formulation of the cosmetic composition of the present invention is a suspension, a liquid diluent such as water, ethanol or propylene glycol, an ethoxylated isostearyl alcohol, a suspending agent such as polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tracanth and the like may be used.

When the formulation of the cosmetic composition of the present invention is surfactant-containing cleansing, as carrier components, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate , fatty acid amide ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linolin derivatives or ethoxylated glycerol fatty acid esters, and the like can be used.

The cosmetic composition of the present invention can be applied to skin, lotion, cream, essence, pack, foundation, color cosmetics, sunscreen, two-way cake, face powder, compact, makeup base, skin cover, eye shadow, lipstick, lip gloss, lip fix, eyebrow pencil , It can be applied to cosmetics such as lotion and detergents such as shampoo and soap.

The cosmetic composition according to an embodiment of the present invention may further include functional additives and ingredients included in general cosmetic compositions, in addition to the extracts extracted from the mugwort and triticale. The functional additive may include a component selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high-molecular peptides, high-molecular polysaccharides, sphingolipids, and seaweed extracts.

In addition to the above functional additives, the cosmetic composition of the present invention may further contain components included in general cosmetic compositions as needed. Ingredients other than those included include fats and oils, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, bactericides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, fragrances, blood circulation accelerators, cooling agents, antiperspirants, purified water and the like.

Hereinafter, the present invention will be described in more detail through examples. However, the above embodiments and experimental examples are presented as examples of the present invention, and detailed descriptions thereof are omitted if it is determined that detailed descriptions of well-known techniques or configurations may unnecessarily obscure the gist of the present invention. It can be done, and the present invention is not limited thereby. Various modifications and applications of the present invention are possible within the scope of the claims described below and equivalents interpreted therefrom.

<Preparation Example 1> Preparation of mugwort extract

For the mugwort extract used in this experiment, 2 g of freeze-dried mugwort was extracted by reflux cooling in distilled water at 40 ° C for 2 hours, which was freeze-dried and used in the experiment.

<Preparation Example 2> Preparation of Sambaekcho extract

The extract used in this experiment was extracted by reflux cooling for 2 hours in distilled water at 40 ℃ 2 g of lyophilized Sambyeongcho, and it was freeze-dried and used in the experiment.

<Example 1> Materials and methods

1-1. Preparation of mixed extracts of mugwort and sambaekcho

The mixed extract used in this experiment is a mixture of the mugwort extract prepared by the method of Preparation Example 1 and the triticale extract prepared by the method of Preparation Example 2 at a weight ratio of 2:8, 4:6, 6:4, and 8:2 It was manufactured.

1-2. cell culture

Nasal cells (RPMI2650) used in this experiment were purchased from the Korea Cell Line Bank (Seoul, Korea), and were supplemented with 10% fetal bovine serum (FBS) and 1% penicillin (50 units/mL)/streptomycin (100 μg/mL). It was cultured using Roswell Park Memorial Institute (RPMI1640) medium containing Lung cells (A549) were purchased from the American Type Culture Collection (ATCC, Manassas, VA, USA), and were treated with 10% bovine calf serum (CS) and 1% penicillin (50 units/mL)/streptomycin (100 μg/mL). Dulbecco's modified Eagle medium was used as a culture medium and cultured under 5% CO ₂ conditions at 37°C.

1-3. Cell viability measurement

To measure cell viability, samples and ultrafine dust pretreated cells were treated with MTT stock solution (10 mg/mL) and reacted for 2 hours. The generated formazan crystals were melted at room temperature for 20 minutes by removing all the medium and adding dimethyl sulfoxide, and then using a microplate reader (Epoch 2, BioTek Instruments Inc., Winooski, VT, USA) to detect 570 nm (determination wave) and 650 nm (reference wave) was measured for absorbance.

1-4. Measurement of ROS production content in cells

Intracellular ROS generation inhibitory effect was divided into 1×10 ⁴ cells/well in a 96-well plate and cultured for 24 hours. After 24 hours of incubation, the sample was treated by exchanging with a medium containing 0.5% FBS or CS, and after 30 minutes, ultrafine dust (PM _2.5 ) was pretreated to a final concentration of 100 μg / mL and cultured for 24 hours. Then, 50 μM dichlorofluorescin diacetate was treated and reacted for 40 minutes, and fluorescence intensity was measured at 485 nm (excitation wave) and 535 nm (emission wave) using a fluorescence photometer (Infinite F200, Tecan, Mannedorf, Switzerland).

1-5. Preparation of animal models

The animals used in this experiment were 6-week-old male BALB/c mice purchased from Samtako (Osan, Korea), maintained at a temperature of 22±2°C and relative humidity of 50±5%, and provided with sufficient water and feed. The breeding environment was maintained. All experiments were performed under the approval of the Animal Experiment Ethics Committee of Gyeongsang National University (IACUC approval number: GNU-190530-M0028). Experimental animals were brought in for 1 week after undergoing an adaptation period, and then divided into a control group, an ultrafine dust group (PM2.5), and a sample diet group, and were bred for 15 weeks. The ultrafine dust group and the sample diet group were exposed to fine dust in the whole body exposure chamber, and the normal control group was injected with filtered air. After dissolving the extract in drinking water, the sample group was orally administered at concentrations of 50 and 100 mg/kg of body weight before exposure.

1-6. Measurement of Superoxide dismutase (SOD) activity in mouse tissue

The homogenate obtained by homogenizing the tissue with Phosphate buffered saline (PBS) was centrifuged (400 ×g, 5 minutes, 4°C), and the supernatant was removed to obtain a pellet. 1×cel extraction buffer [10×SOD buffer 0.5 mL, 20% triton X-100 0.1 mL, distilled water 4.4 mL, phenylmethanesulfonyl fluoride in ethanol 5 μL] was added to the pellet, and extraction was performed on ice for 30 minutes. The extract was centrifuged (10,000 × g, 10 minutes, 4° C.), and the SOD content of the supernatant was measured using a SOD assay kit (Sigma-Aldrich Chemical Co.).

1-7. Measurement of reduced glutathione (reduced GSH) activity in mouse tissue

The reduced GSH content was measured by adding 10 times the volume of PBS to the extracted lung tissue, homogenizing it, and then centrifuging (10,000 × g, 15 minutes, 4 ° C), and the obtained supernatant was used in the experiment. The same amount of 30% metaphosphoric acid was added to the supernatant to remove the interfering protein by centrifugation at 2,000 × g, and the supernatant was sifted again to contain 0.2M Tris hydrochloric acid buffer (pH 7.8) and 0.65 N sodium hydroxide, 1mg. After adding OPT (in methanol) at a concentration of / mL and reacting at room temperature for 15 minutes by blocking light, fluorescence was measured at 1-minute intervals at an excitation wave of 320 nm and an emission wave of 420 nm using a fluorescence photometer.

1-8. Measurement of lipid peroxide content in tissues

In order to measure lipid peroxide (malondialdehyde, MDA) in the tissue, the lung tissue was separated by sacrificing the experimental animals. Phosphate-buffered saline was added to the separated lung tissue and homogenized using a bullet blender (Next Advance Inc., Averill Park, NY, USA), and the supernatant was obtained by centrifugation (10,000 × g, 10 minutes, 4°C). used in the experiment. In the supernatant, 1% phosphoric acid and 0.67% thiobarbituric acid (TBA) were mixed and reacted in a water bath (95 °C) for 1 hour. The absorbance of the resulting MDA-TBA complex was measured at 532 nm. The MDA content was expressed as the content per mg protein by substituting into the standard curve.

1-9. Biomarker analysis in serum

After the end of the behavioral test, the blood collected from the abdominal vena cava of the experimental animals was centrifuged (10,000 × g, 10 minutes, 4° C.) to separate the serum for biomarker analysis in the serum. Serum lactate dehydrogenase (LDH) was analyzed using a serum analyzer (Fuji dri-chem 4000i, Fuji film Co., Tokyo, Japan). FRAP activity of serum was measured by mixing serum with FRAP reagent [0.3 M sodium acetate buffer (pH 3) + 10 mM 2,4,6-tripyridyl-S-triazine (TPTZ) solution dissolved in 40 mM HCl + 20 mM FeCl3 solution]. After that, the mixture was reacted in the dark for 30 minutes, and absorbance was measured at 593 nm.

1-10. Mitochondrial isolation and activity measurement

To isolate tissue mitochondria, homogenize by adding an isolation buffer [215 mM manitol, 75 mM sucrose, 0.1% BSA, 20 mM HEPES (Na+), pH7.2] containing 1 mM ethylene glycol tetraacetic acid (EGTA). Homogenized lung tissue was centrifuged (1,300 × g, 5 min, 4 °C). Pellet added isolation buffer containing 1mM EGTA and 0.1% digitonin, reacted on ice for 5 minutes, centrifuged (13,000 × g, 10 minutes, 4°C), and used the final pellet as mitochondria in lung tissue for experiments did

To measure ROS content in mitochondria, the isolated mitochondrial extract was mixed with KCI-based respiration buffer (125 mM potassium chloride, 2 mM potassium phosphate, 20 mM HEPES, 1 mM magnesium chloride, 500 μM EGTA, 2.5 mM malate and 5 mM pyruvate) and 25 μM DCF-DA for 20 minutes. After the reaction, it was measured at 485 nm (excitation wave) and 535 nm (emission wave) using a fluorescence photometer.

To measure mitochondrial membrane potential (MMP), assay solution [5 mM pyruvate, 5mM malate in isolation buffer] and 1 μM JC-1 dye were mixed in a black 96-well and reacted for 20 minutes in a dark room. After the reaction, fluorescence intensity was measured at 530 nm (excitation wave) and 590 nm (emission wave) using a fluorescence photometer.

To measure the ATP content in mitochondria, add 1% TCA solution to the separated mitochondria, leave them on ice, and then add 25mM sodium acetate buffer (pH 7.4). The ATP level of the supernatant was measured on a luminometer using an ATP assay kit (Promega, Madison, WI, USA).

1-11. Protein expression level measurement

Tissues were homogenized using RIPA solution (ProtinExTM Animal cell/tissue, GeneAll Biotechnology, Seoul, Korea) containing 1% protease inhibitor cocktail (Thermo Fisher Scientific, Rockford, IL, USA). The homogenized tissue was centrifuged (13,000 × g, 15 minutes, 4°C) and the supernatant was used for the experiment. The supernatant mixed with loading buffer (5×) was pretreated by reacting at 95°C for 7 minutes, and the protein was separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Then, it was transferred to a poly-vinylidene difluoride (PVDF) membrane (Millipore, Billerica, MA, USA). The protein-transferred PVDF membrane was blocked with a 5% skim milk (Sigma-Aldrich Co., St. Louis, MO, USA) solution and reacted with diluted primary antibody (1:1,000) at 4°C for 10 hours. . The reacted membrane was washed three times in a tris-buffered saline solution containing 0.1% Tween 20 and reacted with the secondary antibody at room temperature. Bands were expressed on the membrane using chemiluminescence (Bionote, Hwaseong, Korea) and measured using the iBright™ CL1000 Imaging System (Thermo Fisher, Waltham, MA, USA).

1-12. statistical processing

All experiments were expressed as mean ± standard deviation, and the significance of each average value was verified by SAS Software 9.4 (SAS Institute Inc., Cary, NC, USA) and Duncan's multiple range test. Significant differences between samples were verified at the 5% level (p < 0.05).

<Example 2> Experimental results

2-1. Cell viability measurement result of single extract of mugwort or sambaekcho

The results of confirming the cell protective effect of the mugwort extract and the sambaekcho extract on RPMI2650 cells (nasal cavity) and A549 cells (lung) from toxicity caused by fine dust are shown in FIG. 1 .

As a result of the experiment, it was confirmed that the protection effect of the mugwort extract was relatively better than that of the sambaekcho extract when compared at low concentrations. However, in the case of mugwort extract, it was confirmed that there is cytotoxicity in RPMI2650 cells at high concentration (FIG. 1A). In contrast, the cytoprotective effect of the extract of Sambaekcho was not relatively superior to that of the mugwort extract, but there was no cytotoxicity at high concentrations, and it was confirmed that the cell viability increased from cytotoxicity caused by ultrafine dust in a concentration-dependent manner (Fig. 1C, D) .

2-2. Cell protection effect of mixed extracts of mugwort and sambaekcho

In order to establish an optimal mixing ratio of the mixed extracts of mugwort and sambaekcho, cell viability was measured by mixing at various ratios. The same concentration (100 μg / A cytotoxicity test was performed with mL), and the results are shown in FIG. 2.

As a result of the experiment, in the case of the mixed extract of mugwort and Sambakcho in RPMI2650 cells, it was confirmed that the cell viability increased compared to the single extract (0:10, 10:0) (Fig. 2A), and in the case of A549 cells, the higher ratio of mugwort It was confirmed that the cell protection effect due to fine dust was high (FIG. 2B). In particular, the mixed extract in which mugwort and Sambaekcho were mixed at a weight ratio of 6:4 in nasal cells was significantly superior in cell protection effect compared to mixed extracts with other mixing ratios (2:8, 4:6, 8:2). Confirmed.

2-3. LC/MS-MS Analysis of Mixed Extracts of Wormwood and Sambakcho

Through Example 2-2, the material analysis of the mixed extract (AASC) in which mugwort and Sambakcho were mixed at a weight ratio of 6: 4, which was confirmed to be relatively excellent in cell protection effect due to toxicity of fine dust, was performed. The results are shown in Figure 3 as follows.

As a result of UPLC/Q-TOF-MS/MS analysis, Quinic acid (RT: 0.77, m/z: 192.05), Chlorogenic acid (RT: 2.83, m/z: 354.08), Isoschaftoside (RT: 2.97, m/z: 564.14), Rutin (RT: 3.12, m/z: 478.07), Quercetin-3-Glucuronide (RT: 3.21, m/z: 478.07), 3,4-dicaffeoyl quinic acid (RT: 3.29, m/z: 516.12 ), 3,5-Dicaffeoyl quinic acid (RT: 3.35, m/z: 516.12), and 4,5-Dicaffeoyl quinic acid (RT: 3.40, m/z: 516.12) were identified, and dicaffeoyl was the most abundant substance. It has been identified as an isomer of quinic acid.

2-4. Antioxidant efficacy of mixed extracts of mugwort and sambaekcho

Changes in biochemicals related to oxidative stress of lung tissue due to ultrafine dust were confirmed, and the results are shown in Table 1 below.

As a result of the experiment, it was confirmed that oxidative stress increased in lung tissue. Malondialdehyde (MDA) is a lipid peroxide and is also used as a major marker of oxidative stress. In the lung tissue of the ultrafine dust group, it was confirmed that MDA increased significantly compared to the normal control group, and superoxide dismutase (SOD) and reduced GSH ( reduced glutathione) was confirmed to be significantly reduced compared to the normal control group. In other words, oxidative stress increased in lung tissue when ultrafine dust was exposed for a long time. In contrast, in the AASC-administered group, it was confirmed that MDA was significantly decreased, and antioxidant enzymes, superoxide dismutase (SOD) and reduced GSH (reduced glutathione), were confirmed to be increased. These results mean that the mixed extract of mugwort and sambaekcho suppressed the increased oxidative stress caused by ultrafine dust.

Control PM AASC 50 AASC 100 MDA contents
(nmole/mg of protein) 1.34 ± ^0.04b 1.47 ± 0.05 ^a 1.30 ± ^0.10b 1.31 ± ^0.08b SOD contents
(U/mg of protein) 5.14 ± 0.41 ^a 4.17 ± ^0.17b 4.67 ± ^0.39ab 4.63 ± ^0.31ab Reduced Glutathione
(% of control) 100.0 ± 24.0 ^a 61.0 ± ^12.1b 77.8 ± ^8.4ab 74.8 ± ^7.2ab

Results are indicated as mean ± SD (n = 9). Different small letters represent statistical difference ( p < 0.05) of each group in a high order.

Subsequently, ferric reducing antioxidant power (FRAP) activity in serum was confirmed, and the results are shown in Table 2 below. FRAP activity indicates the antioxidant activity of serum, and lactate dehydrogenase (LDH) is an indicator that can indicate the degree of oxidative damage.

As a result of the experiment, it was confirmed that the FRAP activity of the ultrafine dust group decreased and the level of LDH increased.

Control PM AASC 50 AASC 100 FRAP activity
(Absorbance at 593 nm) 0.43 ± 0.02 ^a 0.28 ± ^0.01c 0.31 ± ^0.01c 0.35 ± ^0.03b LDH contents (U/L) 187.3± ^23.8ab 256.0 ± 42.8 ^a 146.3 ± ^33.3b 186.0 ± ^34.4ab

Results are indicated as mean ± SD (n = 9). Different small letters represent statistical difference ( p < 0.05) of each group in a high order.

2-5. Effect of Mitochondrial Dysfunction Improvement of Mixed Extracts of Mugwort and Sambaekcho

The results of mitochondrial function evaluation of lung tissue are shown in Table 3 below. As a result of the experiment, in the case of the ultrafine dust group, compared to the control group, an increase in the level of reactive oxygen species (ROS) inside the mitochondria and a decrease in the mitochondrial membrane potential (MMP) and ATP levels were confirmed. These results indicate that mitochondrial dysfunction is caused by ultrafine dust. However, in the mugwort and Sambakcho mixed extract (AASC)-administered group, which was orally administered with the mugwort and Sambakcho mixed extract, a decrease in the level of ROS and a significant increase in the MMP and ATP levels were confirmed. It has been confirmed that it improves mitochondrial dysfunction caused by fine dust.

Control PM AASC 50 AASC 100 ROS contents
(% of control) 100.0 ± ^26.5b 136.4 ± 25.5 ^a 112.6 ± ^32.6ab 107.6 ± ^20.3ab MMPs
(% of control) 100.0 ± 14.4 ^{b c} 74.1 ± 26.4 ^c 118.5 ± ^31.9ab 149.7 ± 5.9 ^a ATP contents
(nmole/mg) 306.8 ± 21.4 ^a 170.2 ± ^53.9b 241.1± ^56.4ab 310.0 ± 63.2 ^a

Results are indicated as mean ± SD (n = 9). Different small letters represent statistical difference ( p < 0.05) of each group in a high order.

2-6. Anti-inflammatory efficacy of mixed extracts of mugwort and sambaekcho

The results of confirming changes in the expression of inflammation-related proteins in lung tissue and olfactory bulb tissue are shown in FIG. 4 . As a result of the experiment, it was confirmed that the expression of p-JNK, p-IκB-α, p-NF-κB and inflammatory cytokines increased in the ultrafine dust group. An increase in phosphorylated JNK indirectly shows an increase in the inflammatory response, and an increase in phosphorylation of IκB-α and NF-kB, an increase in inflammatory cytokines TNF-a and IL-1B, and an increase in the expression of COX-2 are ultrafine dust. indicates an increase in inflammation. On the other hand, in the AASC-administered group that ingested the mixed extract of mugwort and Sambakcho, the increase in inflammation caused by ultrafine dust was found to be significantly recovered. These results show that ingestion of the mixed extract of mugwort and Sambakcho is effective in improving inflammation in lung tissue and olfactory bulb tissue caused by ultrafine dust. These results alleviate the toxicity caused by ultrafine dust, and mean that the mixed extract of mugwort and 300 plant can be used for the prevention and treatment of inflammatory respiratory diseases.

As described above, the specific embodiments of the present invention have been described in detail, but those skilled in the art who understand the spirit of the present invention may add, change, delete, etc. other components within the scope of the same idea, and other degenerate inventions. However, other embodiments included within the scope of the present invention can be easily suggested. Therefore, the embodiments described above should be understood as illustrative in all respects and not limiting. The scope of the present invention is indicated by the claims to be described later rather than the above detailed description, and all changes or modifications derived from the meaning and scope of the claims and equivalent concepts thereof are included in the scope of the present invention. should be interpreted as

Claims (10)

A pharmaceutical composition for preventing or treating inflammatory respiratory diseases caused by ultrafine dust containing a mixed extract of mugwort and sagebrush.
According to claim 1,
The mixed extract is characterized in that it is prepared by extracting mugwort or sagebrush with a solvent selected from the group consisting of water, lower alcohols having 1 to 4 carbon atoms, and mixed solvents thereof, preventing or treating inflammatory respiratory diseases caused by ultrafine dust pharmaceutical composition for use.
According to claim 1,
The mixed extract is a pharmaceutical composition for preventing or treating inflammatory respiratory diseases caused by ultrafine dust, characterized in that mugwort and sambaekcho are mixed in a weight ratio of 6: 4.
According to claim 1,
The respiratory disease is any one selected from the group consisting of pneumonia, asthma, chronic bronchitis, pneumoconiosis, tuberculosis, emphysema, chronic obstructive pulmonary disease, cystic fibrosis, cough, phlegm, sore throat, tonsillitis, sinusitis, rhinitis, bronchiolitis obliterans and laryngitis That is, a pharmaceutical composition for preventing or treating inflammatory respiratory diseases caused by ultrafine dust.
According to claim 1,
The mixed extract is characterized by suppressing malondialdehyde and increasing superoxide dismutase and reduced glutathione, preventing inflammatory respiratory diseases caused by ultrafine dust or Therapeutic pharmaceutical composition.
According to claim 1,
The mixed extract is a pharmaceutical composition for preventing or treating inflammatory respiratory diseases caused by ultrafine dust, characterized in that for improving mitochondrial dysfunction caused by ultrafine dust.
According to claim 1,
The mixed extract is characterized by suppressing the increase of p-JNK, p-IκB-α, p-NF-κB, TNF-α, IL-1β and COX-2 due to ultrafine dust, to ultrafine dust A pharmaceutical composition for preventing or treating inflammatory respiratory diseases caused by
Health functional food composition for preventing or improving inflammatory respiratory diseases caused by ultrafine dust containing a mixed extract of mugwort and sagebrush.
A health food composition for preventing or improving inflammatory respiratory diseases caused by ultrafine dust containing a mixed extract of mugwort and sambaekcho.
A cosmetic composition for preventing or improving skin inflammation caused by ultrafine dust, comprising a mixed extract of mugwort and sambaekcho.

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