WO2019098615A1 - Composition containing aster k oraiensis extract or fraction thereof for prevention or treatment of dry eye - Google Patents
Composition containing aster k oraiensis extract or fraction thereof for prevention or treatment of dry eye Download PDFInfo
- Publication number
- WO2019098615A1 WO2019098615A1 PCT/KR2018/013646 KR2018013646W WO2019098615A1 WO 2019098615 A1 WO2019098615 A1 WO 2019098615A1 KR 2018013646 W KR2018013646 W KR 2018013646W WO 2019098615 A1 WO2019098615 A1 WO 2019098615A1
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- WO
- WIPO (PCT)
- Prior art keywords
- dry eye
- extract
- fraction
- eye syndrome
- prevention
- Prior art date
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Images
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
Definitions
- the present invention relates to a pharmaceutical composition for preventing or treating dry eye syndrome comprising extracts of Echinochloa or its fractions as an active ingredient, a health functional food for preventing or ameliorating dry eye syndrome containing extracts of Echinochloa crus-galli and fractions thereof as an active ingredient, And a method for preventing or treating dry eye syndrome, comprising the step of administering to the individual a composition, and a foliar extract or a fraction thereof.
- Dry eye syndrome is not simply a tear defect, but it causes eye discomfort, eye fatigue, decreased visual acuity, and instability of the tear layer due to inflammation of the tear and ocular surface (cornea and conjunctiva) .
- inflammation plays an important role in infiltration of inflammatory cells, increased expression of immune activation molecules and adhesion molecules, Th1 and Th17 responses, abnormalities of apoptotic markers and chemokines have.
- dry eye syndrome is a common disease that occurs in about 20% of adults in Korea.
- the global warming due to global climate change especially El Ni ⁇ o phenomenon, and environmental pollution such as fine dust.
- dry eye syndrome and eye fatigue related functional foods are being imported in large quantities overseas.
- functional food products developed in Korea are prevented from being transferred to eye fatigue and dry eye syndrome, it is possible to prevent national health loss as well as national financial loss.
- Aster koraiensis is a perennial herb that belongs to Asteraceae . It grows in light and moist wetlands, and is a Korean specialty plant native to South Gyeonggi City and Jeju Island in Korea. It is often used mainly for gardening or in the field of jigging. It is sometimes used for the treatment of sputum and asthma by boiling soft leaves, eating herbs or roots.
- the inventors of the present invention completed the present invention by confirming that the extract of Echinochloa or its fractions can treat dry eye syndrome through an increase of tear secretion amount, inhibition of corneal morphological change and increase of mucin secretion amount.
- Another object of the present invention is to provide a health functional food for preventing or ameliorating dry eye syndrome, which comprises extracts of Euphorbiaceae or fractions thereof as an active ingredient.
- Another object of the present invention is to provide an eye cosmetic additive composition for preventing or ameliorating dry eye syndrome comprising extracts of Echinochloa or a fraction thereof as an active ingredient.
- Another object of the present invention is to provide a method for preventing or treating dry eye syndrome, comprising the step of administering an extract of Echinochloa or a fraction thereof.
- the extract of Eisenhower extract of the present invention and its fractions can significantly reduce the amount of tear secretion due to dry eye syndrome and the change of corneal morphology, and thus can be widely used for the development of pharmaceutical compositions for the prevention or treatment of dry eye syndrome.
- FIG. 1 is a graph showing a quantitative change in the amount of tear secretion according to the administration of the extract of Echinochloa crus-galli (*: p ⁇ 0.05 vs. Normal; #: p ⁇ 0.05 vs. dry eye).
- FIG. 2 is a photograph showing changes in the corneal morphology of rats following the administration of Echinacea purpurea extract.
- FIG. 3 is a photograph (A) showing a change in the amount of corneal mucin secretion in rats according to the administration of Echinacea purpurea extract and a graph (B) showing a quantitative analysis thereof (***: p ⁇ eye).
- the inventors of the present invention discovered that the extract of Echinosophora koreensis or its fraction exhibited the effect of treating dry eye syndrome in various studies in order to develop a therapeutic agent capable of effectively treating dry eye syndrome. These extracts or fractions showed a similar effect to that of commercial drugs used for the treatment of dry eye syndromes, as well as a significant decrease in the amount of tear secretion and changes in corneal morphology depending on dry eye syndrome.
- the technique for treating dry eye syndrome using the extracts or fractions thereof has not been known at all and has been developed for the first time by the present inventors.
- the present invention provides a pharmaceutical composition for preventing or treating dry eye syndrome, which comprises extracts of Euphorbiaceae or fractions thereof as an active ingredient.
- the present invention provides a composition for preventing or treating dry eye syndrome, comprising the extract of Euphorbiaceae or a fraction thereof as an active ingredient.
- the extracts of the eyelashes having the preventive and therapeutic activity of dry eye syndrome can be extracted from various organs of natural, hybrid, and variant plants, and can be extracted from various organs such as roots, stems, leaves, flowers, It can be extracted from the culture.
- Aster koraiensis used in the present invention is a perennial plant belonging to Asteraceae . It grows in a light and moist wetland, and is a Korean specialty plant native to South Gyeonggi province and Jeju Island in Korea. It is often used mainly for gardening or in the field of jigging. It is sometimes used for the treatment of sputum and asthma by boiling soft leaves, eating herbs or roots.
- the extract of Echocardioptera can be extracted from roots, stems, leaves, flowers, or fruits of Echinochloa sp., And is not particularly limited thereto.
- the extract of Eisenhower extract includes, but is not limited to, extracts with a solvent selected from the group consisting of water, lower alcohols having 1 to 4 carbon atoms, and mixed solvents thereof.
- the above extract may contain any one of the extract obtained by the extraction treatment, the diluted solution or the concentrate of the extract, the dried product obtained by drying the extract, or the adjusted product or the purified product.
- the pharmaceutical composition may contain, for example, 0.001 to 100% by weight, relative to the total weight of the total composition, and specifically, 0.000005 to 80% by weight, but is not limited thereto.
- the alcohol may be butyl alcohol, ethyl alcohol, methyl alcohol or a water-soluble alcohol thereof.
- the water-soluble alcohol may be an alcohol in an amount of 0.1 to 100% by weight.
- fraction means a product obtained by performing fractionation to separate a specific component or a specific component group from a mixture containing various components.
- the fractionation method for obtaining the fraction in the present invention is not particularly limited and may be carried out according to a method commonly used in the art.
- a method in which a fraction obtained from the extract is treated with a predetermined solvent by treating the extract obtained by extracting the Eisenhower extract.
- the fraction may be a hexane fraction, an ethyl acetate fraction, a butanol fraction, or a water fraction of Echinacea purpurea extract.
- the fractions may each comprise 0.01 to 100% by weight, more specifically 1 to 80% by weight, based on the total weight of the pharmaceutical composition.
- the kind of the fraction solvent used for obtaining the fraction in the present invention is not particularly limited, and any solvent known in the art can be used.
- Non-limiting examples of the fraction solvent include polar solvents such as water and alcohol; And non-polar solvents such as hexane, ethyl acetate, chloroform, and dichloromethane. These may be used alone or in combination of two or more.
- polar solvents such as water and alcohol
- non-polar solvents such as hexane, ethyl acetate, chloroform, and dichloromethane. These may be used alone or in combination of two or more.
- a C 1 to C 4 alcohol may be specifically used.
- dry eye syndrome refers to dry eye syndrome, which is caused by inflammation of the lacrimal gland and decongestion of the cornea, inhibiting tear secretion, And abnormal conjunctival epithelial disorder caused by excessive dryness of the tears due to the dry eye syndrome and resulting in wounds of the cornea.
- prevention refers to any act that inhibits or delays the symptoms of dry eye syndrome by administration of a composition comprising the extract of Eisenhower extract according to the present invention or a fraction thereof.
- treatment refers to any action that alleviates or alleviates the symptoms of dry eye syndrome upon administration of a composition comprising the extract of Eisenhower extract according to the present invention or a fraction thereof.
- the composition may be to increase or maintain or maintain the amount of tear secretion, inhibit corneal morphological changes, promote mucin secretion, or improve eye fatigue.
- the morphological change of the cornea may be due to excessive irritation of the tears, which may cause the surface of the cornea to become rugged and the rounded circle to warp and distort.
- the composition of the present invention may improve smoothness and flatness.
- the mucin secretion promoting means that mucin secretion component, which is one of the components of tears, is increased. Reduction of the amount of mucin secretion causes irregularity of tear film and can cause dry eye syndrome through reduction in quality of tears
- the composition of the present invention may promote mucin secretion to stably maintain the tear film.
- the term " pharmaceutical composition" means a preparation intended for the prevention or treatment of disease, and may be formulated into various forms according to each ordinary method. For example, it can be formulated into a form such as powders, granules, tablets, capsules, suspensions, emulsions, syrups and the like, and can be formulated in the form of external preparations, suppositories and sterilized injection solutions.
- the pharmaceutical composition of the present invention may be in the form of an external preparation for eyeball, that is, a form suitable for topical administration, and may be formulated into, for example, eye drops, creams, ointments, gels or lotions.
- composition of the present invention may be prepared in the form of a pharmaceutical composition for preventing or treating dry eye syndrome, which further comprises an appropriate carrier, excipient or diluent conventionally used in the production of a pharmaceutical composition, (non-naturally occuring carrier).
- the carrier, excipient and diluent which may be contained in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, Calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
- a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used.
- Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, Sucrose, lactose, gelatin and the like.
- lubricants such as magnesium stearate and talc are also used.
- Liquid preparations for oral use may include various excipients such as wetting agents, sweetening agents, fragrances, preservatives, etc.
- Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories.
- the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like.
- the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
- the dosage of the pharmaceutical composition of the present invention can be determined by those skilled in the art in consideration of the purpose of use, the degree of addiction to the disease, the age, body weight, sex, history, or kind of the substance used as the active ingredient.
- the pharmaceutical composition of the present invention may be administered at a dose of from about 0.1 ng to about 1,000 mg / kg, in particular from 1 ng to 1,000 mg / kg, per adult, and the frequency of administration of the composition of the present invention is specifically limited However, it may be administered once a day or divided into several doses. The dose is not intended to limit the scope of the invention in any way.
- the present invention provides a method for treating dry eye syndrome comprising administering the pharmaceutical composition to a subject suffering from dry eye syndrome in a pharmaceutically effective amount.
- individual as used herein may include, without limitation, mammals including rats, livestock, and the like with dry eye syndrome.
- the " individual” may include companion animals.
- the companion animal refers to an animal living together with a human, and specific examples include, but are not limited to, mammals such as dogs, cats, hamsters, and guinea pigs, and birds such as parrots and canaries.
- composition may be administered in single or multiple doses in a pharmaceutically effective amount.
- the administration route of the pharmaceutical composition for preventing or treating dry eye syndrome of the present invention can be administered through any ordinary route as long as it can reach the target tissue.
- composition of the present invention may be administered orally, intraperitoneally, intramuscularly, subcutaneously, intradermally, transdermal patch, oral, intranasal, intrapulmonary, Intramuscular administration, intrathecal administration, intrarectal administration, and the like, and specifically administered orally.
- the present invention provides a health functional food for preventing or ameliorating dry eye syndrome comprising extracts of Euphorbiaceae or fractions thereof as an active ingredient.
- Echinacea purpurea extract, fraction, and dry eye syndrome is as defined above.
- improvement means any action that alters or modifies dryness of the eye by orally administering the composition.
- the term "functional" as used in the present invention means that the structure and function of the human body have a beneficial effect for health use such as controlling nutrients or physiological action.
- the health functional food of the present invention can be prepared by a method commonly used in the art and can be prepared by adding raw materials and ingredients that are conventionally added in the art.
- the formulation of the health functional food may also be produced without limitation as long as the formulation is recognized as a health functional food.
- the health functional food of the present invention can be manufactured in various forms, and unlike general pharmaceuticals, it has advantages of being free from side effects that may occur when a food is used as a raw material for a long period of time, and is excellent in portability, Can be ingested as an adjuvant to improve the effect of preventing or improving dry eye syndrome.
- the health functional food is a food prepared by adding the extract of the present invention or a fraction thereof to a food material such as a beverage, a tea, a spice, a gum or a confection, or encapsulated, powdered, or a suspension, But it has the advantage that there is no side effect that can occur when a drug is taken for a long time using a food as a raw material, unlike a general medicine.
- an eye cosmetic additive composition for preventing or improving dry eye syndrome comprising extracts of Euphorbiaceae or fractions thereof as an active ingredient.
- the definition of the extract of Eisenhower extract, fraction, dry eye syndrome, prevention and improvement in the eye cosmetic additive composition is as defined above.
- the additive may be included in eye care products and may be effective in preventing or ameliorating the diseases.
- the composition may include eye make-up products.
- eye make-up products include eye pencil, Liner, eye shadow, mascara, and eye makeup remover.
- a quasi-drug composition for preventing or improving dry eye syndrome comprising extracts of Euphorbiaceae or fractions thereof as an active ingredient.
- quasi-drug product in the present invention means products which are less active than drugs, for example, for the purpose of diagnosing, treating, improving, alleviating, treating or preventing a disease in a human or an animal.
- Quasi-drugs are products that are not used for medicines, such as fibers and rubber products used for the treatment and prevention of diseases of humans and animals, and are not acting directly or indirectly on the human body, These include sterilization and insecticides to prevent infectious diseases.
- the type and formulations of the quasi-drug composition of the present invention are not particularly limited, but may be disinfectant cleaner, shower foam, gagrin, wet tissue, detergent soap, hand wash, humidifier filler, mask, ointment or filter filler.
- a feed composition for preventing or ameliorating dry eye syndrome comprising extracts of Euphorbiaceae or fractions thereof as an active ingredient.
- feed means any natural or artificial diet, single meal or the like or ingredients of the above formula for ingesting, ingesting, digesting or suitable for the individual.
- the kind of the feed is not particularly limited, and feeds conventionally used in the art can be used.
- feeds include vegetable feeds such as cereals, muscle roots, food processing busines logistics, algae, fibers, pharmaceuticals, buses, oils, pastes, pulses or cereals; Animal feeds such as proteins, inorganic substances, fats, oils, fats, oils, monocellular proteins, animal plankton or foods. These may be used alone or in combination of two or more.
- extracts or fractions thereof are useful as pharmaceutical compositions for the prevention or treatment of dry eye diseases, dry eye dryness, health functional foods for preventing or improving eye fatigue, eye cosmetic additives, quasi-drug compositions and feed compositions .
- the experimental group consisted of the following: non-invasive normal group (NOR) with no abnormality, the disease caused by dry eye lacrimal gland by the method of Example 2.1 (ASKO-100), 250 mg / kg of ASKO (ASKO), and ASKO-100 (ASKO-100) administered with 100 mg / kg of the extract of Aspergillus oryzae of the present invention 250), the drug administration group (ASKO-500) in which 500 mg / kg of the extract of the present invention (ASKO) was administered.
- the drug comprising the extract of Eisenhower extract of the present invention was prepared by dissolving the above dose in sterilized physiological saline containing 0.5% DMSO, followed by oral administration for 4 days, followed by additional administration for 5 days for dry eye syndrome for 3 days. On the 7th day after total administration, the animals were anesthetized and the change in color of the test strip was measured by tearing after 30 seconds of contact with the phenol-red thread volume test (FCI Opthalmics Zone Quick, Japan) And the efficacy of the drug was evaluated.
- the morphological changes of the cornea according to the administration of the extract of Echinacea purpurea were confirmed using the experimental animal of Example 2.1 to confirm the effect of the Echinochloa crus-galli extract on dry eye syndrome.
- composition of the test group and administration of the drug were carried out in the same manner as in Example 2.2.
- the animals were anesthetized and photographed using a stereoscopic microsope (Olympus, Japan) equipped with a fiberoptic ring illuminator. Changes in corneal morphology were assessed by grading the degree of distortion of the rounded circle shape of the circular light reflected on the corneal epithelium from 0 to 5. 0 point: No distortion, 1 point: Distortion at 1/4 point, 2 points: Distortion at 2/4 point, 3 points: Distortion at 3/4 point, 4 points: Distortion at all points, 5 point: Distortion at severe point Can not recognize the shape of the round circle.
- the morphological changes of the cornea were evaluated.
- the tears secreted from the external lacrimal gland formed a tear film, and the smooth and flat surface state was maintained.
- FIG. 2 Respectively.
- abnormalities in the tear film covering the cornea resulted in degeneration of the epithelium of the corneal epithelium and smooth surface of the cornea, so that the rounded shape was warped and distorted.
- ASKO-500 it was confirmed that the corneal morphological changes such as the disease group were suppressed, thereby reflecting a shape close to the circular shape (Fig. 2).
- composition of the test group and administration of the drug were carried out in the same manner as in Example 2.2.
- Immunostaining was performed using a mucin4 antibody on the corneal tissue slides.
- the mucin 4 expression level in the dry eye disease group was significantly decreased in the corneal surface, compared with that in the normal group in which the amount of mucin 4 was large.
- the expression level of the drug-treated group was significantly increased in the ASKO-500 concentration group as compared with the dry eye disease group, and it was found that the concentration was increased in a concentration-dependent manner.
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Abstract
The present invention relates to: a pharmaceutical composition containing an Aster koraiensis extract or a fraction thereof as an active ingredient for prevention or treatment of dry eye; a health functional food, an eye cosmetic additive composition, and a quasi drug composition each containing an Aster koraiensis extract or a fraction thereof as an active ingredient for prevention or treatment of dry eye; and a method for prevention or treatment of dry eye, the method comprising a step for administering an Aster koraiensis extract or a fraction thereof to an individual. The Aster koraiensis extract or the fraction thereof of the present invention can significantly suppress a decrease in the amount of tear secretion, a change in corneal morphology, and a decrease in the amount of mucin secretion, and thus can be widely utilized in the development of a pharmaceutical composition for prevention or treatment of dry eye.
Description
본 발명은 벌개미취 추출물 또는 이의 분획물을 유효성분으로 포함하는 안구건조증 예방 또는 치료용 약학 조성물, 벌개미취 추출물 또는 이의 분획물을 유효성분으로 포함하는 안구건조증 예방 또는 개선용 건강기능식품, 눈 화장료 첨가제 조성물 및 의약외품 조성물, 및 벌개미취 추추물 또는 이의 분획물을 개체에 투여하는 단계를 포함하는 안구건조증 예방 또는 치료방법에 관한 것이다.The present invention relates to a pharmaceutical composition for preventing or treating dry eye syndrome comprising extracts of Echinochloa or its fractions as an active ingredient, a health functional food for preventing or ameliorating dry eye syndrome containing extracts of Echinochloa crus-galli and fractions thereof as an active ingredient, And a method for preventing or treating dry eye syndrome, comprising the step of administering to the individual a composition, and a foliar extract or a fraction thereof.
안구 건조증(건성안: dry eye syndrome)은 단순히 눈물부족이 아닌, 눈물과 안구표면(각막 및 결막)의 염증에 의한 안구의 불편감, 눈피로, 시력저하, 눈물층의 불안정성을 유발하여 안구표면에 손상을 주어, 통증, 불규칙한 각막 표면, 흐리고 변동폭이 커진 시력 및 각막궤양 등의 발병 위험성이 크다. 그러나 이러한 발병기전은 아직 완전히 규명되지 않았으나, 염증세포의 침윤, 면역활성화 분자 및 접착분자발현 증가, Th1 및 Th17 반응, 세포사멸 마커 및 케모카인의 비정상적인 변화 등 염증이 중요한 역할을 한다는 연구결과가 보고되고 있다. Dry eye syndrome is not simply a tear defect, but it causes eye discomfort, eye fatigue, decreased visual acuity, and instability of the tear layer due to inflammation of the tear and ocular surface (cornea and conjunctiva) , There is a great risk of pain, irregular corneal surface, blurred vision, increased corneal ulceration, and the like. However, the mechanisms of this pathogenesis have not yet been fully elucidated, but studies have shown that inflammation plays an important role in infiltration of inflammatory cells, increased expression of immune activation molecules and adhesion molecules, Th1 and Th17 responses, abnormalities of apoptotic markers and chemokines have.
일반적으로 안구 건조증 치료를 위해서 칼륨과 안토시아닌이 풍부한 음식섭취를 권장하고 있고, 이외에도 케일, 키위, 사과 등의 과일섭취도 적극 권장하고 있다, 또한 인공눈물 점안, 눈물점을 막아 배출되는 눈물의 양을 조절하는 치료법을 사용하기도 한다. In general, it is recommended to consume foods rich in potassium and anthocyanins for the treatment of dry eye syndrome. In addition, fruits such as kale, kiwi and apple are also highly recommended, and the amount of tears released by artificial tear drops and tear points They also use controlled treatments.
글로벌 데이터 보고서에 의하면 세계 안구건조증 시장은 2012년 16억 달러 (1조8816억원)에서 2011년에는 55억 달러(6조4680억원)로 연평균 12.8%의 성장률을 보일 것을 전망하였다. 건강보험심사평가원 자료에 의하면 국내 안구건조증 치료에 사용된 총 진료비는 연평균 8.6%씩 증가해 2009년에는 521억원, 2013년에는 726억원으로 5년 사이 200억원 이상 증가하였다(이투데이, 2016. 06.27).According to the Global Data Report, the world market for dry eye syndrome is expected to grow at a CAGR of 12.8% from US $ 1.6 billion in 2012 (US $ 1.88 trillion) to US $ 5.5 billion (US $ 6.4 trillion) in 2011. According to the Health Insurance Review and Assessment Service, total medical expenses used for the treatment of dry eye syndrome increased by 8.6% per year, reaching 52.1 billion won in 2009 and 72.6 billion won in 2013 (over 2 million won) .
그러나 안구건조증은 우리나라 성인의 20% 내외로 발생하는 흔한 질병으로, 특히 전 세계적인 기후 변화 특히 엘리뇨 현상으로 온도가 올라가고 있는 상황과 미세먼지 등 환경오염으로 인해 안구건조증 환자가 지속적으로 증가하고 있으며, 증가하는 수요에 맞춰 현재 해외에서 안구건조증이나 눈 피로 관련 기능성식품이 대량 수입되고 있는 상황이다. 국내에서 우수한 기능성 식품이 개발될 경우 눈피로, 안구건조증으로 이행되는 것을 예방함으로 국민 개인의 건강뿐만 아니라 막대한 국가 재정 손실을 방지할 수 있다.However, dry eye syndrome is a common disease that occurs in about 20% of adults in Korea. In particular, the global warming due to global climate change, especially El Niño phenomenon, and environmental pollution such as fine dust, In order to meet the demand, dry eye syndrome and eye fatigue related functional foods are being imported in large quantities overseas. When functional food products developed in Korea are prevented from being transferred to eye fatigue and dry eye syndrome, it is possible to prevent national health loss as well as national financial loss.
또한 국내 반려동물 동물용의약품 시장 규모는 2006년 3천8백억원에서 2013년 5천4백억원 시장을 형성하고 있으며, 2015년 기준 6천 5백억원으로 매년 4% 가량의 성장하고 있는 성장 잠재력이 무궁무진한 시장이다 (전자신문 2016.08.10). 반려견의 안구건조증의 경우 거의 모든 연령대 반려견에서 발생하는 가장 흔한 안질환으로 약 35%의 반려견에서 발생 되는 것으로 보고 (Journal of Veterinary clinics 557-562, 2007) 되었고, 전문치료제로는 옵티뮨 (안연고)이 FDA에 동물용으로 승인 받은 유일한 전문치료제이며, 대부분은 인체용 전문의약품을 그대로 사용하고 있는 실정이다. In addition, the domestic animal animal drug market is expected to grow from KRW 380 billion in 2006 to KRW 54 billion in 2013, and KRW 650 billion in 2015, which is growing at an annual rate of 4% It is market (electronic newspaper 2016.08.10). In the case of dry eye syndrome, it is the most common eye disease occurring in almost all aged dogs. It is reported in about 35% of the dogs (Journal of Veterinary Clinics 557-562, 2007), and Opti- It is the only specialty treatment approved by the FDA for use in animals, and most of them use specialty medicines for human use.
벌개미취(Aster koraiensis)는 국화과(Asteraceae)에 속하는 다년생 초본으로 빛이 잘 들고 물기가 많은 습지 등에서 자라며, 한국의 경기도 이남 및 제주도에서 자생하는 한국의 특산식물이다. 주로 원예용 또는 지피용으로 사용되는 경우가 많으며, 연한 잎을 삶아 나물로 먹거나, 뿌리를 달여 가래 및 천식에 대한 치료 용도로 사용되는 경우도 있다. Aster koraiensis is a perennial herb that belongs to Asteraceae . It grows in light and moist wetlands, and is a Korean specialty plant native to South Gyeonggi Province and Jeju Island in Korea. It is often used mainly for gardening or in the field of jigging. It is sometimes used for the treatment of sputum and asthma by boiling soft leaves, eating herbs or roots.
본 발명자들은 벌개미취 추출물 또는 이의 분획물이 눈물 분비량의 증가, 각막형태 변화의 억제 및 뮤신 분비량의 증가를 통해 안구건조증을 치료할 수 있음을 확인하여, 본 발명을 완성하였다.The inventors of the present invention completed the present invention by confirming that the extract of Echinochloa or its fractions can treat dry eye syndrome through an increase of tear secretion amount, inhibition of corneal morphological change and increase of mucin secretion amount.
본 발명의 하나의 목적은 벌개미취 추출물 또는 이의 분획물을 유효성분으로 포함하는 안구건조증 예방 또는 치료용 약학 조성물을 제공하는 것이다.It is an object of the present invention to provide a pharmaceutical composition for preventing or treating dry eye syndrome comprising extracts of Euphorbiaceae or fractions thereof as an active ingredient.
본 발명의 다른 하나의 목적은 벌개미취 추출물 또는 이의 분획물을 유효성분으로 포함하는 안구건조증 예방 또는 개선용 건강기능식품을 제공하는 것이다.Another object of the present invention is to provide a health functional food for preventing or ameliorating dry eye syndrome, which comprises extracts of Euphorbiaceae or fractions thereof as an active ingredient.
본 발명의 또 다른 하나의 목적은 벌개미취 추출물 또는 이의 분획물을 유효성분으로 포함하는 안구건조증 예방 또는 개선용 눈 화장료 첨가제 조성물을 제공하는 것이다.Another object of the present invention is to provide an eye cosmetic additive composition for preventing or ameliorating dry eye syndrome comprising extracts of Echinochloa or a fraction thereof as an active ingredient.
본 발명의 또 다른 하나의 목적은 벌개미취 추출물 또는 이의 분획물을 유효성분으로 포함하는 안구건조증 예방 또는 개선용 의약외품 조성물을 제공하는 것이다.It is another object of the present invention to provide a quasi-drug composition for preventing or ameliorating dry eye syndrome comprising extracts of Euphorbiaceae or fractions thereof as an active ingredient.
본 발명의 또 다른 하나의 목적은 벌개미취 추출물 또는 이의 분획물을 투여하는 단계를 포함하는 안구건조증 예방 또는 치료방법을 제공하는 것이다.Another object of the present invention is to provide a method for preventing or treating dry eye syndrome, comprising the step of administering an extract of Echinochloa or a fraction thereof.
본 발명의 벌개미취 추출물 및 이의 분획물은 안구건조증에 의한 눈물 분비량의 감소 및 각막 형태의 변화를 유의하게 억제할 수 있으므로, 안구건조증의 예방 또는 치료를 위한 약학 조성물의 개발에 널리 활용될 수 있을 것이다.The extract of Eisenhower extract of the present invention and its fractions can significantly reduce the amount of tear secretion due to dry eye syndrome and the change of corneal morphology, and thus can be widely used for the development of pharmaceutical compositions for the prevention or treatment of dry eye syndrome.
도 1은 벌개미취 추출물 투여에 따른 눈물 분비량 변화를 정량적으로 나타낸 그래프이다 (*: p<0.05 vs. Normal; #: p<0.05 vs. dry eye).FIG. 1 is a graph showing a quantitative change in the amount of tear secretion according to the administration of the extract of Echinochloa crus-galli (*: p <0.05 vs. Normal; #: p <0.05 vs. dry eye).
도 2는 벌개미취 추출물 투여에 따른 랫트의 각막형태 변화를 나타내는 사진이다.FIG. 2 is a photograph showing changes in the corneal morphology of rats following the administration of Echinacea purpurea extract.
도 3은 벌개미취 추출물 투여에 따른 랫트의 각막 뮤신 분비량 변화를 나타낸 사진(A) 및 이를 정량적으로 나타낸 그래프(B)이다 (***: p<0.001 vs. Normal; #: p<0.05 vs. dry eye).FIG. 3 is a photograph (A) showing a change in the amount of corneal mucin secretion in rats according to the administration of Echinacea purpurea extract and a graph (B) showing a quantitative analysis thereof (***: p < eye).
본 발명자들은 안구건조증을 효과적으로 치료할 수 있는 치료제를 개발하고자, 다양한 연구를 수행하던 중, 벌개미취 추출물 또는 이의 분획물이 안구건조증을 치료하는 효과를 나타냄을 발견하였다. 상기 벌개미취 추출물 또는 분획물은 안구 건조증에 따라 나타나는 눈물 분비량의 감소 및 각막 형태의 변화를 유의하게 억제할 뿐만 아니라, 안구건조증의 치료를 위해 사용되고 있는 상용약물과 유사한 효과를 나타냄을 알 수 있었다. 상기 벌개미취 추출물 또는 분획물을 사용하여 안구건조증을 치료하는 기술은 지금까지 전혀 알려져 있지 않고, 본 발명자에 의하여 최초로 개발되었다. The inventors of the present invention discovered that the extract of Echinosophora koreensis or its fraction exhibited the effect of treating dry eye syndrome in various studies in order to develop a therapeutic agent capable of effectively treating dry eye syndrome. These extracts or fractions showed a similar effect to that of commercial drugs used for the treatment of dry eye syndromes, as well as a significant decrease in the amount of tear secretion and changes in corneal morphology depending on dry eye syndrome. The technique for treating dry eye syndrome using the extracts or fractions thereof has not been known at all and has been developed for the first time by the present inventors.
상기 목적을 달성하기 위한 일 실시양태로서, 본 발명은 벌개미취 추출물 또는 이의 분획물을 유효성분으로 포함하는 안구건조증 예방 또는 치료용 약학 조성물을 제공한다.As one embodiment for achieving the above object, the present invention provides a pharmaceutical composition for preventing or treating dry eye syndrome, which comprises extracts of Euphorbiaceae or fractions thereof as an active ingredient.
또한, 본 발명은 벌개미취 추출물 또는 이의 분획물을 유효성분으로 포함하는 조성물의 안구건조증 예방 또는 치료 용도를 제공한다. In addition, the present invention provides a composition for preventing or treating dry eye syndrome, comprising the extract of Euphorbiaceae or a fraction thereof as an active ingredient.
안구건조증의 예방 및 치료 활성을 갖는 상기 벌개미취 추출물은 천연, 잡종, 변종 식물의 다양한 기관으로부터 추출될 수 있고, 예를 들어 뿌리, 줄기, 잎, 꽃, 열매의 몸통, 열매의 껍질뿐만 아니라 식물 조직 배양물로부터 추출 가능하다.The extracts of the eyelashes having the preventive and therapeutic activity of dry eye syndrome can be extracted from various organs of natural, hybrid, and variant plants, and can be extracted from various organs such as roots, stems, leaves, flowers, It can be extracted from the culture.
본 발명에서 사용된 용어, "벌개미취(Aster koraiensis)"는 국화과(Asteraceae)에 속하는 다년생 초본으로 빛이 잘 들고 물기가 많은 습지 등에서 자라며, 한국의 경기도 이남 및 제주도에서 자생하는 한국의 특산식물이다. 주로 원예용 또는 지피용으로 사용되는 경우가 많으며, 연한 잎을 삶아 나물로 먹거나, 뿌리를 달여 가래 및 천식에 대한 치료 용도로 사용되는 경우도 있다.The term " Aster koraiensis " used in the present invention is a perennial plant belonging to Asteraceae . It grows in a light and moist wetland, and is a Korean specialty plant native to South Gyeonggi Province and Jeju Island in Korea. It is often used mainly for gardening or in the field of jigging. It is sometimes used for the treatment of sputum and asthma by boiling soft leaves, eating herbs or roots.
본 발명에서, 상기 벌개미취 추출물은 벌개미취의 뿌리, 줄기, 잎, 꽃, 또는 열매로부터 추출한 것일 수 있으며, 이에 특별히 제한되는 것은 아니다.In the present invention, the extract of Echocardioptera can be extracted from roots, stems, leaves, flowers, or fruits of Echinochloa sp., And is not particularly limited thereto.
본 발명에서, 상기 벌개미취 추출물은 물, 탄소수 1 내지 4의 저급 알콜 및 이들의 혼합 용매로 구성되는 군으로부터 선택되는 용매로 추출한 것을 포함하나, 이에 제한되지 않는다. 또한, 본 발명에 있어서, 상기 추출물에는, 추출처리에 의해 얻어지는 추출액, 추출액의 희석액 또는 농축액, 추출액을 건조하여 얻어지는 건조물, 또는 이들 조정제물 또는 정제물 중 어느 하나도 포함될 수 있다.In the present invention, the extract of Eisenhower extract includes, but is not limited to, extracts with a solvent selected from the group consisting of water, lower alcohols having 1 to 4 carbon atoms, and mixed solvents thereof. In addition, in the present invention, the above extract may contain any one of the extract obtained by the extraction treatment, the diluted solution or the concentrate of the extract, the dried product obtained by drying the extract, or the adjusted product or the purified product.
상기 약학적 조성물은 벌개미취 추출물을 총 조성물의 중량 대비 0.000001 내지 100 중량%로 포함할 수 있으며, 구체적으로는 0.000005 내지 80 중량% 포함할 수 있으나, 이에 제한된 것은 아니다.The pharmaceutical composition may contain, for example, 0.001 to 100% by weight, relative to the total weight of the total composition, and specifically, 0.000005 to 80% by weight, but is not limited thereto.
상기 알콜은 부틸 알콜, 에틸 알콜, 메틸 알콜 또는 이의 수용성 알콜인 것일 수 있다. 구체적으로 상기 수용성 알콜은 알콜이 0.1 내지 100 % 중량 범위로 포함되는 것 일 수 있다.The alcohol may be butyl alcohol, ethyl alcohol, methyl alcohol or a water-soluble alcohol thereof. Specifically, the water-soluble alcohol may be an alcohol in an amount of 0.1 to 100% by weight.
본 발명에서 사용되는 용어, "분획물"은 여러 다양한 구성 성분들을 포함하는 혼합물로부터 특정 성분 또는 특정 성분 그룹을 분리하기 위하여 분획을 수행하여 얻어진 결과물을 의미한다.The term " fraction " as used herein means a product obtained by performing fractionation to separate a specific component or a specific component group from a mixture containing various components.
본 발명에서 상기 분획물을 얻는 분획 방법은 특별히 제한되지 아니하며, 당해 기술 분야에서 통상적으로 사용하는 방법에 따라 수행될 수 있다. 상기 분획 방법의 비제한적인 예로는, 벌개미취 추출물을 추출하여 얻은 추출물에 소정의 용매를 처리하여 상기 추출물로부터 분획물을 얻는 방법을 들 수 있다.The fractionation method for obtaining the fraction in the present invention is not particularly limited and may be carried out according to a method commonly used in the art. As a non-limiting example of the above-mentioned fractionation method, there can be mentioned a method in which a fraction obtained from the extract is treated with a predetermined solvent by treating the extract obtained by extracting the Eisenhower extract.
본 발명에 있어서, 상기 분획물은 벌개미취 추출물의 헥산 분획물, 에틸 아세테이트 분획물, 부탄올 분획물 또는 물 분획물인 것일 수 있다. 상기 분획물은 각각 약학 조성물의 총 중량에 대하여 0.01 내지 100 중량%, 보다 구체적으로 1 내지 80 중량%로 포함될 수 있다.In the present invention, the fraction may be a hexane fraction, an ethyl acetate fraction, a butanol fraction, or a water fraction of Echinacea purpurea extract. The fractions may each comprise 0.01 to 100% by weight, more specifically 1 to 80% by weight, based on the total weight of the pharmaceutical composition.
본 발명에서 상기 분획물을 얻는 데에 사용되는 분획 용매의 종류는 특별히 제한되지 아니하며, 당해 기술 분야에서 공지된 임의의 용매를 사용할 수 있다. 상기 분획 용매의 비제한적인 예로는 물, 알코올 등의 극성 용매; 헥산(Hexan), 에틸 아세테이트(Ethyl acetate), 클로로포름(Chloroform), 디클로로메탄(Dichloromethane) 등의 비극성 용매 등을 들 수 있다. 이들은 단독으로 사용되거나 2 종 이상 혼합하여 사용될 수 있다. 상기 분획 용매 중 알코올을 사용하는 경우에는 구체적으로 C1 내지 C4의 알코올을 사용할 수 있다.The kind of the fraction solvent used for obtaining the fraction in the present invention is not particularly limited, and any solvent known in the art can be used. Non-limiting examples of the fraction solvent include polar solvents such as water and alcohol; And non-polar solvents such as hexane, ethyl acetate, chloroform, and dichloromethane. These may be used alone or in combination of two or more. When an alcohol is used in the fraction solvent, a C 1 to C 4 alcohol may be specifically used.
본 발명에서 사용된 용어 "안구건조증"이란, 안구건조증(dry eye syndrome)은 눈물샘의 염증 및 각막의 탈신경화에 의하여 눈물 분비가 억제되거나 마이봄선의 기능부전(Meibomian gland dysfunction) 또는 눈꺼풀의 기능이상에 따른 비정상적인 눈물 증발 등에 의하여 발생하는 질환일 수 있고, 상기 안구건조증에 의해 눈물이 과다 건조되어 각막의 상처로 나타나는 각결막 상피장애일 수 있다.As used herein, the term " dry eye syndrome " refers to dry eye syndrome, which is caused by inflammation of the lacrimal gland and decongestion of the cornea, inhibiting tear secretion, And abnormal conjunctival epithelial disorder caused by excessive dryness of the tears due to the dry eye syndrome and resulting in wounds of the cornea.
본 발명에서 사용된 용어 "예방"이란, 본 발명에 따른 벌개미취 추출물 또는 이의 분획물을 포함하는 조성물의 투여로 안구건조증의 증상을 억제 또는 지연시키는 모든 행위를 말한다.As used herein, the term " prevention " refers to any act that inhibits or delays the symptoms of dry eye syndrome by administration of a composition comprising the extract of Eisenhower extract according to the present invention or a fraction thereof.
본 발명에서 사용된 용어 "치료"란, 본 발명에 따른 벌개미취 추출물 또는 이의 분획물을 포함하는 조성물의 투여로 상기 안구건조증의 증상이 호전되거나 이롭게 변경되는 모든 행위를 말한다.As used herein, the term " treatment " refers to any action that alleviates or alleviates the symptoms of dry eye syndrome upon administration of a composition comprising the extract of Eisenhower extract according to the present invention or a fraction thereof.
본 발명에서 상기 조성물은 눈물 분비량을 증가 또는 보존, 유지 시키거나 각막 형태 변화를 억제하거나, 뮤신 분비를 촉진시키거나, 눈피로를 개선하는 것인 것일 수 있다. In the present invention, the composition may be to increase or maintain or maintain the amount of tear secretion, inhibit corneal morphological changes, promote mucin secretion, or improve eye fatigue.
상기 각막의 형태 변화는 눈물의 과다건조로 인해 각막의 표면이 울퉁불퉁해져 둥근 원형이 휘어지고 찌그러지는 형태를 나타내는데 본 발명의 조성물은 이를 매끈하고 평평하게 개선시키는 것일 수 있다.The morphological change of the cornea may be due to excessive irritation of the tears, which may cause the surface of the cornea to become rugged and the rounded circle to warp and distort. The composition of the present invention may improve smoothness and flatness.
상기 뮤신 분비 촉진은 눈물의 구성 요소 중 하나인 점액질의 성분인 뮤신의 분비량이 증가하는 현상을 의미하며, 뮤신의 분비량 감소는 눈물막의 불균형을 야기하여 눈물의 질적인 감소를 통해 안구건조증을 유발할 수 있는데 본 발명의 조성물은 뮤신 분비를 촉진하여 눈물막을 안정적으로 유지시키는 것일 수 있다.The mucin secretion promoting means that mucin secretion component, which is one of the components of tears, is increased. Reduction of the amount of mucin secretion causes irregularity of tear film and can cause dry eye syndrome through reduction in quality of tears The composition of the present invention may promote mucin secretion to stably maintain the tear film.
본 발명의 일 실시예에서는 벌개미취 추출물을 투여하여, 고농도군에서 유의적으로 눈물 분비량이 증가함을 확인하였고, 농도의존적으로 그 효과가 증가하는 것을 확인하였다(도 1). In one embodiment of the present invention, it was confirmed that the tear secretion was significantly increased in the high concentration group and the effect was increased in a dose-dependent manner (FIG. 1).
본 발명의 다른 일 실시예에서는 벌개미취 추출물을 투여하여, 고농도군에서 안구건조증 질환군에서 나타나는 각막 형태의 변화를 억제함을 확인하였다(도 2).In another embodiment of the present invention, it was confirmed that administration of Echinosophora koreana extract inhibits the change of corneal morphology in the dry eye disease group in the high concentration group (FIG. 2).
본 발명의 또 다른 일 실시예에서는 벌개미취 추출물을 투여하여, 고농도군에서 유의적으로 뮤신 분비량이 증가함을 확인하였고, 농도의존적으로 그 효과가 증가하는 것을 확인하였다(도 3).In another embodiment of the present invention, it was confirmed that mucin secretion was significantly increased in the high concentration group by administering the extract of Echinosophora koreensis, and the effect was increased in a concentration-dependent manner (FIG. 3).
따라서, 상기 결과를 통해서 벌개미취 추출물이 안구건조증에 대해 치료효과를 가짐을 알 수 있었다.Therefore, it can be seen from the above results that the extract of Echinosophora koreensis has a therapeutic effect on dry eye syndrome.
본 발명에서 사용된 용어 "약학 조성물"이란, 질병의 예방 또는 치료를 목적으로 제조된 것을 의미하며, 각각의 통상의 방법에 따라 다양한 형태로 제형화하여 사용될 수 있다. 예컨대, 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽 등의 제형으로 제형화할 수 있고, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 구체적으로, 본 발명의 약학 조성물은 안구 외용제형, 즉 점안투여하기 적합한 형태일 수 있으며, 예를 들어, 점안제, 크림제, 연고제, 겔제 또는 로션제로 제형화하여 사용될 수 있으나, 이에 제한된 것은 아니다.As used herein, the term " pharmaceutical composition " means a preparation intended for the prevention or treatment of disease, and may be formulated into various forms according to each ordinary method. For example, it can be formulated into a form such as powders, granules, tablets, capsules, suspensions, emulsions, syrups and the like, and can be formulated in the form of external preparations, suppositories and sterilized injection solutions. Specifically, the pharmaceutical composition of the present invention may be in the form of an external preparation for eyeball, that is, a form suitable for topical administration, and may be formulated into, for example, eye drops, creams, ointments, gels or lotions.
상기 본 발명의 조성물은, 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 또는 희석제를 추가로 포함하는 안구건조증 예방 또는 치료용 약학 조성물의 형태로 제조될 수 있는데, 상기 담체는 비자연적 담체(non-naturally occuring carrier)를 포함할 수 있다. The composition of the present invention may be prepared in the form of a pharmaceutical composition for preventing or treating dry eye syndrome, which further comprises an appropriate carrier, excipient or diluent conventionally used in the production of a pharmaceutical composition, (non-naturally occuring carrier).
본 발명에서, 상기 약학 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다.In the present invention, the carrier, excipient and diluent which may be contained in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, Calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 상엽 추출물과 이의 분획물들에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스티레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는 데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, Sucrose, lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use may include various excipients such as wetting agents, sweetening agents, fragrances, preservatives, etc. in addition to water and liquid paraffin, which are simple diluents commonly used in suspension, liquid solutions, emulsions and syrups have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
본 발명의 약학 조성물의 투여량은 사용목적, 질환의 중독도, 환자의 연령, 체중, 성별, 기왕력, 또는 유효성분으로서 사용되는 물질의 종류 등을 고려하여 당업자가 결정할 수 있다. 예를 들어, 본 발명의 약학 조성물은 성인 1인당 약 0.1 ng 내지 약 1,000mg/kg, 구체적으로 1 ng 내지 약 1,000mg/kg로 투여할 수 있고, 본 발명의 조성물의 투여빈도는 특별히 이에 제한되지 않으나, 1일 1회 투여하거나 또는 용량을 분할하여 수회 투여할 수 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The dosage of the pharmaceutical composition of the present invention can be determined by those skilled in the art in consideration of the purpose of use, the degree of addiction to the disease, the age, body weight, sex, history, or kind of the substance used as the active ingredient. For example, the pharmaceutical composition of the present invention may be administered at a dose of from about 0.1 ng to about 1,000 mg / kg, in particular from 1 ng to 1,000 mg / kg, per adult, and the frequency of administration of the composition of the present invention is specifically limited However, it may be administered once a day or divided into several doses. The dose is not intended to limit the scope of the invention in any way.
다른 하나의 양태로서, 본 발명은 상기 약학 조성물을 약제학적으로 유효한 양으로 안구 건조증이 발병된 개체에 투여하는 단계를 포함하는 안구 건조증의 치료방법을 제공한다. In another aspect, the present invention provides a method for treating dry eye syndrome comprising administering the pharmaceutical composition to a subject suffering from dry eye syndrome in a pharmaceutically effective amount.
본 발명에서 사용된 용어 "개체"란 안구건조증이 발병된 쥐, 가축 등을 포함하는 포유동물 등을 제한 없이 포함할 수 있다.The term " individual " as used herein may include, without limitation, mammals including rats, livestock, and the like with dry eye syndrome.
보다 구체적으로, 상기 "개체"는 반려동물을 포함할 수 있다. 상기 반려동물은 인간과 함께 더불어 사는 동물을 의미하며, 구체적인 종류로서 개, 고양이, 햄스터, 기니피그 등의 포유류, 앵무새, 카나리아 등의 조류 등을 들 수 있으나, 이에 제한되는 것은 아니다.More specifically, the " individual " may include companion animals. The companion animal refers to an animal living together with a human, and specific examples include, but are not limited to, mammals such as dogs, cats, hamsters, and guinea pigs, and birds such as parrots and canaries.
상기 조성물은 약학적으로 유효한 양으로 단일 또는 다중 투여될 수 있다.The composition may be administered in single or multiple doses in a pharmaceutically effective amount.
본 발명의 안구건조증의 예방 또는 치료용 약학 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 어떠한 일반적인 경로를 통하여도 투여될 수 있다. The administration route of the pharmaceutical composition for preventing or treating dry eye syndrome of the present invention can be administered through any ordinary route as long as it can reach the target tissue.
본 발명의 약학 조성물은 특별히 이에 제한되지 않으나, 목적하는 바에 따라 점안 투여, 복강내 투여, 정맥내 투여, 근육내 투여, 피하 투여, 피내 투여, 경피패치투여, 경구 투여, 비내 투여, 폐내 투여, 직장내 투여 등의 경로를 통해 투여 될 수 있고, 구체적으로 경구 투여의 경로를 통해 투여될 수 있다. The pharmaceutical composition of the present invention may be administered orally, intraperitoneally, intramuscularly, subcutaneously, intradermally, transdermal patch, oral, intranasal, intrapulmonary, Intramuscular administration, intrathecal administration, intrarectal administration, and the like, and specifically administered orally.
본 발명의 또 다른 하나의 양태로서, 본 발명은 벌개미취 추출물 또는 이의 분획물을 유효성분으로 포함하는 안구건조증 예방 또는 개선용 건강기능식품을 제공한다.In another aspect of the present invention, the present invention provides a health functional food for preventing or ameliorating dry eye syndrome comprising extracts of Euphorbiaceae or fractions thereof as an active ingredient.
상기 건강기능식품에서 벌개미취 추출물, 분획물, 및 안구건조증에 대한 정의는 상기 정의된 바와 같다. In the above health functional foods, the definition of Echinacea purpurea extract, fraction, and dry eye syndrome is as defined above.
본 발명에서 사용된 용어 "개선"은 상기 조성물을 경구투여하여 안구건조증이 호전되거나 이롭게 변경되는 모든 행위를 의미한다.As used herein, the term " improvement " means any action that alters or modifies dryness of the eye by orally administering the composition.
본 발명에서 사용된 용어 "기능성"은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건 용도에 유용한 효과를 얻는 것을 의미한다. The term " functional " as used in the present invention means that the structure and function of the human body have a beneficial effect for health use such as controlling nutrients or physiological action.
본 발명의 건강기능식품은 당 업계에서 통상적으로 사용되는 방법에 의하여 제조 가능하며, 상기 제조시에는 당 업계에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 또한, 상기 건강기능식품의 제형 또한 건강기능식품으로 인정되는 제형이면 제한 없이 제조될 수 있다. 본 발명의 건강기능식품은 다양한 형태의 제형으로 제조될 수 있으며, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고 휴대성이 뛰어나므로, 본 발명의 건강기능식품은 안구건조증의 예방 또는 개선의 효과를 증진시키기 위한 보조제로 섭취가 가능하다.The health functional food of the present invention can be prepared by a method commonly used in the art and can be prepared by adding raw materials and ingredients that are conventionally added in the art. In addition, the formulation of the health functional food may also be produced without limitation as long as the formulation is recognized as a health functional food. The health functional food of the present invention can be manufactured in various forms, and unlike general pharmaceuticals, it has advantages of being free from side effects that may occur when a food is used as a raw material for a long period of time, and is excellent in portability, Can be ingested as an adjuvant to improve the effect of preventing or improving dry eye syndrome.
구체적으로, 상기 건강기능식품은 본 발명의 벌개미취 추출물 또는 분획물을 음료, 차류, 향신료, 껌, 과자류 등의 식품 소재에 첨가하거나, 캡슐화, 분말화, 현탁액 등으로 제조한 식품으로, 이를 섭취할 경우 건강상 특정한 효과를 가져오는 것을 의미하나, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용이 없는 장점이 있다.Specifically, the health functional food is a food prepared by adding the extract of the present invention or a fraction thereof to a food material such as a beverage, a tea, a spice, a gum or a confection, or encapsulated, powdered, or a suspension, But it has the advantage that there is no side effect that can occur when a drug is taken for a long time using a food as a raw material, unlike a general medicine.
본 발명의 또 다른 하나의 양태로서, 벌개미취 추출물 또는 이의 분획물을 유효성분으로 포함하는 안구건조증의 예방 또는 개선용 눈 화장료 첨가제 조성물을 제공한다.As another embodiment of the present invention, there is provided an eye cosmetic additive composition for preventing or improving dry eye syndrome comprising extracts of Euphorbiaceae or fractions thereof as an active ingredient.
상기 눈 화장료 첨가제 조성물에서 벌개미취 추출물, 분획물, 안구건조증, 예방 및 개선에 대한 정의는 상기 정의된 바와 같다.The definition of the extract of Eisenhower extract, fraction, dry eye syndrome, prevention and improvement in the eye cosmetic additive composition is as defined above.
상기 첨가제는 눈 화장용 제품류에 포함되어 상기 질환의 예방 또는 개선에 효과를 나타낼 수 있다.본 발명에서 상기 조성물은 눈 화장용 제품류를 포함하는 것일 수 있으며, 상기 눈 화장료 제품류로는 아이브로 펜슬, 아이 라이너, 아이 섀도, 마스카라, 및 아이 메이크업 리무버를 포함하는 군으로부터 선택되는 어느 하나인 것일 수 있다.The additive may be included in eye care products and may be effective in preventing or ameliorating the diseases. In the present invention, the composition may include eye make-up products. Examples of the eye make-up products include eye pencil, Liner, eye shadow, mascara, and eye makeup remover.
본 발명의 또 다른 하나의 양태로서, 벌개미취 추출물 또는 이의 분획물을 유효성분으로 포함하는 안구건조증의 예방 또는 개선용 의약외품 조성물을 제공한다.In another aspect of the present invention, there is provided a quasi-drug composition for preventing or improving dry eye syndrome comprising extracts of Euphorbiaceae or fractions thereof as an active ingredient.
상기 의약외품 조성물에서 벌개미취 추출물, 분획물, 안구건조증, 예방 및 개선에 대한 정의는 상기 정의된 바와 같다. In the above-mentioned quasi-drug composition, the definitions of the extracts of Echinochloa sp., Fractions, dry eye syndrome, prevention and improvement are as defined above.
본 발명에서 용어, "의약외품"은 사람이나 동물의 질병을 진단, 치료, 개선,경감, 처치 또는 예방할 목적으로 사용되는 물품들 중 의약품보다 작용이 경미한 물품들을 의미하는 것으로, 예를 들어 약사법에 따르면 의약외품이란 의약품의 용도로 사용되는 물품을 제외한 것으로, 사람ㆍ동물의 질병 치료나 예방에 쓰이는 섬유 ㆍ고무 제품, 인체에 대한 작용이 경미하거나 직접 작용하지 않으며, 기구 또는 기계가 아닌 것과 이와 유사한 것, 감염병을 막기 위한 살균ㆍ살충제 등이 이에 포함된다. 본 발명의 의약외품 조성물의 종류나 제형은 특별히 제한되지 아니하나, 바람직하게는 소독 청결제, 샤워폼, 가그린, 물티슈, 세제 비누, 핸드 워시, 가습기 충진제, 마스크, 연고제 또는 필터 충진제 등일 수 있다.The term " quasi-drug product " in the present invention means products which are less active than drugs, for example, for the purpose of diagnosing, treating, improving, alleviating, treating or preventing a disease in a human or an animal. For example, Quasi-drugs are products that are not used for medicines, such as fibers and rubber products used for the treatment and prevention of diseases of humans and animals, and are not acting directly or indirectly on the human body, These include sterilization and insecticides to prevent infectious diseases. The type and formulations of the quasi-drug composition of the present invention are not particularly limited, but may be disinfectant cleaner, shower foam, gagrin, wet tissue, detergent soap, hand wash, humidifier filler, mask, ointment or filter filler.
본 발명의 또 다른 하나의 양태로서, 벌개미취 추출물 또는 이의 분획물을 유효성분으로 포함하는 안구건조증의 예방 또는 개선용 사료 조성물을 제공한다.In another aspect of the present invention, there is provided a feed composition for preventing or ameliorating dry eye syndrome comprising extracts of Euphorbiaceae or fractions thereof as an active ingredient.
상기 의약외품 조성물에서 벌개미취 추출물, 분획물, 안구건조증, 예방 및 개선에 대한 정의는 상기 정의된 바와 같다.In the above-mentioned quasi-drug composition, the definitions of the extracts of Echinochloa sp., Fractions, dry eye syndrome, prevention and improvement are as defined above.
본 발명에서 용어, "사료"는 개체가 먹고, 섭취하며, 소화시키기 위한 또는 이에 적당한 임의의 천연 또는 인공 규정식, 한끼식 등 또는 상기 한끼식의 성분을 의미한다.As used herein, the term " feed " means any natural or artificial diet, single meal or the like or ingredients of the above formula for ingesting, ingesting, digesting or suitable for the individual.
상기 사료의 종류는 특별히 제한되지 아니하며, 당해 기술 분야에서 통상적으로 사용되는 사료를 사용할 수 있다. 상기 사료의 비제한적인 예로는, 곡물류, 근과류, 식품 가공 부산물류, 조류, 섬유질류, 제약 부산물류, 유지류, 전분류, 박 류 또는 곡물 부산물류 등과 같은 식물성 사료; 단백질류, 무기물류, 유지류, 광물성류, 유지류, 단세포 단백질류, 동물성 플랑크톤류 또는 음식물 등과 같은 동물성 사료를 들 수 있다. 이들은 단독으로 사용되거나 2종 이상을 혼합하여 사용될 수 있다.The kind of the feed is not particularly limited, and feeds conventionally used in the art can be used. Non-limiting examples of such feeds include vegetable feeds such as cereals, muscle roots, food processing busines logistics, algae, fibers, pharmaceuticals, buses, oils, pastes, pulses or cereals; Animal feeds such as proteins, inorganic substances, fats, oils, fats, oils, monocellular proteins, animal plankton or foods. These may be used alone or in combination of two or more.
본 발명의 일 실시예에서는 벌개미취 추출물을 투여하여, 고농도군에서 유의적으로 눈물 분비량이 증가하는 것과 농도의존적으로 그 효과가 증가하는 것을 확인하였으며(도 1), 벌개미취 추출물을 투여 시 고농도군에서 안구건조증 질환군에서 나타나는 각막 형태의 변화를 억제함을 확인하였으며(도 2), 벌개미취 추출물을 투여하여 고농도군에서 유의적으로 뮤신 분비량이 증가하는 것과 농도의존적으로 그 효과가 증가하는 것을 확인하였다(도 3).In one embodiment of the present invention, it was confirmed that the tear secretion was significantly increased in the high concentration group and the effect was increased in a dose-dependent manner (FIG. 1) (Fig. 2), it was confirmed that the mucin secretion was significantly increased in the high concentration group and the effect was increased in a dose-dependent manner 3).
따라서, 상기 결과를 통해서 벌개미취 추출물 또는 이의 분획물은, 안구건조증 예방 또는 치료용 약학적 조성물, 안구건조증 또는 눈피로 예방 또는 개선용 건강기능식품, 눈 화장료 첨가제, 의약외품 조성물 및 사료 조성물로 유용하게 활용될 수 있음을 알 수 있었다.Accordingly, the extracts or fractions thereof are useful as pharmaceutical compositions for the prevention or treatment of dry eye diseases, dry eye dryness, health functional foods for preventing or improving eye fatigue, eye cosmetic additives, quasi-drug compositions and feed compositions .
이하, 본 발명을 실시예를 통하여 보다 상세하게 설명한다. 그러나 이들 실시예는 본 발명을 예시적으로 설명하기 위한 것으로 본 발명의 범위가 이들 실시예에 한정되는 것은 아니다. Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.
실시예 1. 벌개미취 추출물 제조Example 1: Preparation of extract of chrysanthemum chrysanthemum
벌개미취에 5배량의 정제수를 가하여 95℃에서 5시간동안 추출 후 추출액을 100호 체를 이용하여 여과하였다. 감압농축기를 이용하여 60℃ 이하에서 고형분 25%가 될 때까지 농축 후 농축액에 유당을 넣고 분무건조기 (rpm : 9000, 흡기온도 : 170℃, 배기온도 : 90℃)에서 건조하여 최종적으로 벌개미취 열수 추출물을 시험에 사용하였다. Five times as much purified water was added to the eyelashes and extracted at 95 ° C for 5 hours. The extract was filtered through a No. 100 sieve. The concentrate was concentrated to a solid content of 25% by using a vacuum concentrator at a temperature of 60 ° C or lower. Lactose was added to the concentrate and dried in a spray drier (rpm: 9000, inlet temperature: 170 ° C, exhaust temperature: 90 ° C) Were used for the test.
실시예 2. 실험동물을 이용한 약효시험Example 2. Drug test using an experimental animal
실시예 2.1: 안구건조증 실험동물의 제작Example 2.1: Dry eye syndrome Production of experimental animals
6주령 암컷 SD 랫트(오리엔트바이오, 한국)를 구입하고, 일주일 순화 후, 눈물샘 제거를 위해, 펜토바비탈 나트륨(pentobarbital sodium(30 mg/kg body weight, 한림제약, 한국)으로 마취하였다. 마취시킨 랫트의 안구와 귀 사이 정중앙 부위의 털을 제모하고, 수술부위를 소독한 후 피부를 1cm 가량 절개하였다. 절개 부위로부터 안구 밖 눈물샘(exorbital lacrimal gland)를 떼어낸 후, 피부를 봉합하였다.Six weeks old female SD rats (Orient Bio, Korea) were purchased and anesthetized with pentobarbital sodium (30 mg / kg body weight, Hanlim Pharm., Korea) After removing the exorbital lacrimal gland from the incision site, the skin was sutured. Then, the skin was sutured.
실시예 2.2: 눈물 분비량 측정Example 2.2: Tear secretion measurement
안구건조증에 대한 벌개미취 추출물의 효과를 확인하기 위하여, 상기 실시예 2.1의 실험동물을 이용하여 벌개미취 추출물 투여에 따른 눈물 분비량의 변화를 확인하였다. In order to confirm the effect of the extract of Echinacea purpurea on dry eye syndrome, the change of the amount of tear secretion according to administration of Echinacea extract using the experimental animal of Example 2.1 was confirmed.
각 실험군별로 5마리의 개체를 무작위로 배정하였으며, 실험군은 다음과 같이 구성하였다: 아무 이상이 없는 비수술 정상군 (NOR), 실시예 2.1의 방법으로 안구 밖 눈물샘을 제거하여 안구건조증을 유발시킨 질환군 (DED), 본 발명의 벌개미취 추출물(ASKO)을 100 mg/kg을 투여한 약물투여군 (ASKO-100), 본 발명의 벌개미취 추출물(ASKO)을 250 mg/kg을 투여한 약물투여군 (ASKO-250), 본 발명의 벌개미취 추출물(ASKO)을 500 mg/kg을 투여한 약물투여군 (ASKO-500). 본 발명의 벌개미취 추출물을 포함하는 약물은 0.5 % DMSO가 포함된 멸균 생리식염수에 상기 투여량을 녹여 준비하였으며, 4일 동안 경구 투여 후 투여 5일째 안구건조증을 유발 3일 동안 추가 투여 하였다. 총 투여 7일째 실험동물을 마취 시키고, 페놀-레드 thread 눈물량 검사지(FCI Opthalmics Zone Quick,Japan)를 눈꺼풀 외측 끝 부위 안구표면에 접촉시킨 후 30초 후 눈물에 의해 검사지의 색이 변한 길이를 측정하여 약효 효능 평가를 실시하였다.Five individuals were randomly assigned to each experimental group. The experimental group consisted of the following: non-invasive normal group (NOR) with no abnormality, the disease caused by dry eye lacrimal gland by the method of Example 2.1 (ASKO-100), 250 mg / kg of ASKO (ASKO), and ASKO-100 (ASKO-100) administered with 100 mg / kg of the extract of Aspergillus oryzae of the present invention 250), the drug administration group (ASKO-500) in which 500 mg / kg of the extract of the present invention (ASKO) was administered. The drug comprising the extract of Eisenhower extract of the present invention was prepared by dissolving the above dose in sterilized physiological saline containing 0.5% DMSO, followed by oral administration for 4 days, followed by additional administration for 5 days for dry eye syndrome for 3 days. On the 7th day after total administration, the animals were anesthetized and the change in color of the test strip was measured by tearing after 30 seconds of contact with the phenol-red thread volume test (FCI Opthalmics Zone Quick, Japan) And the efficacy of the drug was evaluated.
그 결과, 도 1에 나타낸 바와 같이, 정상군에서는 눈물량이 많은 것에 비해, 안구건조증 질환군은 눈물량이 유의하게 감소한 것을 확인하였다. 약물 투여군은 안구건조증 질환군과 비교하여 ASKO-250 및 ASKO-500 농도군에서 그 길이가 유의적으로 늘어났으며, 농도의존적으로 증가하는 것을 확인하였다. As a result, as shown in Fig. 1, it was confirmed that the amount of tears was significantly decreased in the dry eye syndrome group compared to that in the normal group. As compared with the dry eye syndrome group, the length of treatment with ASKO-250 and ASKO-500 group was significantly increased, and the dose-dependent increase was observed.
따라서, 상기 결과를 통해서, 벌개미취 추출물을 투여하여 눈물 분비량이 개선됨을 확인하였으므로, 상기 추출물이 안구건조증 치료효과가 있음을 알 수 있었다. Therefore, it was confirmed through the above results that the tear secretion amount was improved by administering the extract of Echinochloa crus-galli, so that the extract had an effect of treating dry eye syndrome.
실시예 2.3: 각막의 형태 변화 측정 Example 2.3: Measurement of morphological change of cornea
안구건조증에 대한 벌개미취 추출물의 효과를 확인하기 위하여, 상기 실시예 2.1의 실험동물을 이용하여 벌개미취 추출물 투여에 따른 각막의 형태 변화를 확인하였다.The morphological changes of the cornea according to the administration of the extract of Echinacea purpurea were confirmed using the experimental animal of Example 2.1 to confirm the effect of the Echinochloa crus-galli extract on dry eye syndrome.
실험군의 구성 및 약물의 투여는 상기 실시예 2.2와 동일하게 수행하였다. The composition of the test group and administration of the drug were carried out in the same manner as in Example 2.2.
각막은 동물을 마취 후, 원형 광섬유 조명기(fiberoptic ring illuminator)가 부착된 입체현미경(stereoscopic microsope, Olympus, Japan)을 이용하여 사진을 찍었다. 각막의 형태 변화는 각막 상피세포에 반사된 원형 조명의 둥근 원 형태에 대한 찌그러짐 정도를 0 내지 5까지 점수를 매겨 평가하였다. 0점: 찌그러짐 없음, 1점: 1/4 부위에서 찌그러짐, 2점: 2/4 부위에서 찌그러짐, 3점: 3/4 부위에서 찌그러짐, 4점: 모든 부위에서 찌그러짐, 5점: 심한 찌그러짐으로 둥근 원형의 형태를 알아볼 수 없음. The animals were anesthetized and photographed using a stereoscopic microsope (Olympus, Japan) equipped with a fiberoptic ring illuminator. Changes in corneal morphology were assessed by grading the degree of distortion of the rounded circle shape of the circular light reflected on the corneal epithelium from 0 to 5. 0 point: No distortion, 1 point: Distortion at 1/4 point, 2 points: Distortion at 2/4 point, 3 points: Distortion at 3/4 point, 4 points: Distortion at all points, 5 point: Distortion at severe point Can not recognize the shape of the round circle.
각막의 형태학적 변화를 평가한 결과, 정상군에서는 외부에 눈물샘에서 분비되는 눈물이 tear film을 형성하여 매끈하고 평평한 표면 상태가 유지됨으로써, 도 2와 같이 원형이 조명 그대로 반사되어 둥근 원모양을 관찰하였다. 그러나 안구건조증 질환군에서는 각막을 덮고 있는 tear film에 이상이 생겨 각막 상피세포의 변성 및 매끈한 각막 표면이 말라서 울퉁불퉁하게 변하게 되어, 둥근 원형이 휘어지고 찌그러지는 형태를 관찰한 반면, ASKO 약물의 고농도 투여군(ASKO-500) 에서는 질환군과 같은 각막형태 변화를 억제하여 원형에 가까운 모양을 반사하는 것을 확인하였다(도 2). The morphological changes of the cornea were evaluated. In the normal group, the tears secreted from the external lacrimal gland formed a tear film, and the smooth and flat surface state was maintained. As a result, as shown in FIG. 2, Respectively. However, in the dry eye syndrome group, abnormalities in the tear film covering the cornea resulted in degeneration of the epithelium of the corneal epithelium and smooth surface of the cornea, so that the rounded shape was warped and distorted. On the other hand, (ASKO-500), it was confirmed that the corneal morphological changes such as the disease group were suppressed, thereby reflecting a shape close to the circular shape (Fig. 2).
따라서, 상기 결과를 통해서, 벌개미취 추출물을 투여하여 안구건조증에 의해 나타나는 각막의 형태변화를 억제함을 확인하였으므로, 상기 추출물이 안구건조증 치료효과가 있음을 알 수 있었다. Accordingly, it was confirmed through the above results that the extract of Eisenhower extract inhibited the morphological change of the cornea caused by dry eye syndrome. Thus, it was found that the extract had an effect of treating dry eye syndrome.
실시예 2.4: 뮤신 분비량 측정Example 2.4: Measurement of mucin secretion amount
안구건조증에 대한 벌개미취 추출물의 효과를 확인하기 위하여, 상기 실시예 2.1의 실험동물을 이용하여 벌개미취 추출물 투여에 따른 각막 점액 단백질인 뮤신의 분비량 변화를 확인하였다.In order to confirm the effect of the extract of Echinacea purpurea on dry eye syndrome, the amount of mucin secreted by the extract of Echinosophora koreensis using the experimental animal of Example 2.1 was examined.
실험군의 구성 및 약물의 투여는 상기 실시예 2.2와 동일하게 수행하였다.The composition of the test group and administration of the drug were carried out in the same manner as in Example 2.2.
각막 조직 슬라이드에서 뮤신4(mucin4) 항체를 이용하여 면역 염색을 수행하였다.Immunostaining was performed using a mucin4 antibody on the corneal tissue slides.
그 결과, 도 3에 나타낸 바와 같이, 정상군에서는 뮤신4 분비량이 많은 것에 비해, 안구건조증 질환군은 각막 표면에서의 뮤신4 발현 수준이 유의하게 감소한 것을 확인하였다. 약물 투여군은 안구건조증 질환군과 비교하여 ASKO-500 농도군에서 그 발현 수준이 유의하게 증가하였으며, 농도 의존적으로 증가하는 것을 확인하였다.As a result, as shown in FIG. 3, it was confirmed that the mucin 4 expression level in the dry eye disease group was significantly decreased in the corneal surface, compared with that in the normal group in which the amount of mucin 4 was large. The expression level of the drug-treated group was significantly increased in the ASKO-500 concentration group as compared with the dry eye disease group, and it was found that the concentration was increased in a concentration-dependent manner.
따라서, 상기 결과를 통해서, 벌개미취 추출물을 투여하는 경우 뮤신 분비가 촉진됨을 확인하였으므로, 상기 추출물이 안구건조증 치료효과가 있음을 알 수 있었다.Therefore, through the above results, it was confirmed that mucin secretion was promoted when the extract of Eisenhower extract was administered, and thus it was found that the extract had an effect of treating dry eye syndrome.
본 명세서는 본 발명의 기술 분야에서 통상의 지식을 가진 자이면 충분히 인식하고 유추할 수 있는 내용은 그 상세한 기재를 생략하였으며, 본 명세서에 기재된 구체적인 예시들 이외에 본 발명의 기술적 사상이나 필수적 구성을 변경하지 않는 범위내에서 보다 다양한 변형이 가능하다. 따라서 본 발명은 본 명세서에서 구체적으로 설명하고 예시한 것과 다른 방식으로 실시될 수 있으며, 이는 본 발명의 기술 분야에 통상의 지식을 가진 자이면 이해할 수 있는 사항이다.It is to be understood that both the foregoing general description and the following detailed description of the present invention are exemplary and explanatory and are intended to provide further explanation of the invention as claimed. More variations are possible within a range that does not. Accordingly, the present invention may be embodied in other ways than those specifically described and illustrated herein, and it may be understood by those skilled in the art.
Claims (10)
- 벌개미취 추출물 또는 이의 분획물을 유효성분으로 포함하는 안구건조증 예방 또는 치료용 약학적 조성물.A pharmaceutical composition for preventing or treating dry eye syndrome, comprising extracts of Echinochloa crus-galli and fractions thereof as an active ingredient.
- 제1항에 있어서,The method according to claim 1,상기 추출물은 물, 탄소수 1내지 4의 저급 알코올 및 이들의 혼합 용매로 구성되는 군으로부터 선택되는 용매로 추출한 추출물인 것인, 약학적 조성물.Wherein the extract is an extract extracted with a solvent selected from the group consisting of water, a lower alcohol having 1 to 4 carbon atoms, and a mixed solvent thereof.
- 제1항에 있어서,The method according to claim 1,상기 분획물은 상기 추출물의 n-헥산 분획물, 에틸 아세테이트 분획물, 부탄올 분획물 또는 물 분획물인 것인, 약학적 조성물.Wherein the fraction is an n-hexane fraction, an ethyl acetate fraction, a butanol fraction or a water fraction of the extract.
- 제1항에 있어서,The method according to claim 1,상기 추출물은 감압고온추출, 열탕추출, 환류추출, 열수추출, 상온추출, 초음파 추출 또는 증기추출 방법으로 추출한 것을 특징으로 하는 안구건조증 예방 및 치료용 약학적 조성물.The pharmaceutical composition for preventing and treating dry eye syndrome according to claim 1, wherein the extract is extracted by a method selected from the group consisting of vacuum, high temperature extraction, hot water extraction, reflux extraction, hot water extraction, room temperature extraction, ultrasonic extraction or steam extraction.
- 제1항에 있어서,The method according to claim 1,상기 조성물은 눈물 분비량을 증가, 보존 또는 유지 시키거나, 각막 형태 변화를 억제하거나, 뮤신 분비를 촉진시키거나, 또는 눈피로를 개선하는 것인, 약학적 조성물.Wherein said composition increases, conserves or maintains tear secretion, inhibits corneal morphological changes, promotes mucin secretion, or improves eye fatigue.
- 제1항에 있어서, 상기 약학적 조성물은 안구 외용제형인 것인, 약학적 조성물.The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is an external preparation for eyeball.
- 벌개미취 추출물 또는 이의 분획물을 유효성분으로 포함하는 안구건조증 예방 또는 개선용 건강기능식품.A health functional food for preventing or ameliorating dry eye syndrome comprising extracts of Echinacea purpurea or fractions thereof as an active ingredient.
- 벌개미취 추출물 또는 이의 분획물을 개체에 투여하는 단계를 포함하는 안구건조증 예방 또는 치료방법.A method for the prevention or treatment of dry eye syndrome comprising the step of administering to a subject an extract of Solanaceae or a fraction thereof.
- 벌개미취 추출물 또는 이의 분획물을 유효성분으로 포함하는 안구건조증의 예방 또는 개선용 눈 화장료 첨가제 조성물.An eye-care cosmetic additive composition for prevention or improvement of dry eye syndrome comprising extracts of Echinochloa crus-galli and fractions thereof as an active ingredient.
- 벌개미취 추출물 또는 이의 분획물을 유효성분으로 포함하는 안구건조증의 예방 또는 치료용 의약외품 조성물.A quasi-drug composition for the prevention or treatment of dry eye syndrome comprising extracts of Euphorbiaceae or fractions thereof as an active ingredient.
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| KR100845469B1 (en) * | 2007-03-09 | 2008-07-10 | 한국 한의학 연구원 | Extract of aster koraiensis, and pharmaceutical compositions and functional food comprising same |
| KR20110038375A (en) * | 2009-10-08 | 2011-04-14 | 한림대학교 산학협력단 | Pharmaceutical composition comprising extract of aster koraiensis for alalgesic |
| KR20120095251A (en) * | 2011-02-18 | 2012-08-28 | 한국과학기술연구원 | Composition comprising the extracts and fractions of gymnaster koraiensis for prevention or treatment of retinal diseases |
| KR20170084845A (en) * | 2016-01-13 | 2017-07-21 | 한국과학기술연구원 | Anti-aging composition comprising aster plant extracts |
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| KR100845469B1 (en) * | 2007-03-09 | 2008-07-10 | 한국 한의학 연구원 | Extract of aster koraiensis, and pharmaceutical compositions and functional food comprising same |
| KR20110038375A (en) * | 2009-10-08 | 2011-04-14 | 한림대학교 산학협력단 | Pharmaceutical composition comprising extract of aster koraiensis for alalgesic |
| KR20120095251A (en) * | 2011-02-18 | 2012-08-28 | 한국과학기술연구원 | Composition comprising the extracts and fractions of gymnaster koraiensis for prevention or treatment of retinal diseases |
| KR20170084845A (en) * | 2016-01-13 | 2017-07-21 | 한국과학기술연구원 | Anti-aging composition comprising aster plant extracts |
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