KR20200117957A - A composition for preventing or treating atopic dermatitis comprising the extract of corn silk - Google Patents
A composition for preventing or treating atopic dermatitis comprising the extract of corn silk Download PDFInfo
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- KR20200117957A KR20200117957A KR1020200128288A KR20200128288A KR20200117957A KR 20200117957 A KR20200117957 A KR 20200117957A KR 1020200128288 A KR1020200128288 A KR 1020200128288A KR 20200128288 A KR20200128288 A KR 20200128288A KR 20200117957 A KR20200117957 A KR 20200117957A
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- KR
- South Korea
- Prior art keywords
- atopic dermatitis
- extract
- prevention
- corn beard
- pharmaceutical composition
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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)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9794—Liliopsida [monocotyledons]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- 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
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- 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
- A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat
Abstract
Description
본 발명은 옥수수수염 추출물을 포함하는 아토피 피부염 예방 또는 치료용 조성물에 관한 것으로, 보다 구체적으로 본 발명은 옥수수수염 추출물 또는 그의 분획물을 포함하는 아토피 피부염 예방 또는 치료용 약학 조성물, 약학 조성물을 개체에 투여하는 단계를 포함하는 아토피 피부염의 치료방법, 옥수수수염 추출물 또는 이의 분획물을 포함하는 아토피 피부염 개선용 식품 조성물, 옥수수수염 추출물 또는 이의 분획물을 포함하는 아토피 피부염의 예방 또는 개선용 의약외품 조성물 및 옥수수수염 추출물 또는 이의 분획물을 포함하는 아토피 피부염의 예방 또는 개선용 화장료 조성물에 관한 것이다.The present invention relates to a composition for preventing or treating atopic dermatitis comprising a corn beard extract, and more specifically, the present invention administering to a subject a pharmaceutical composition for preventing or treating atopic dermatitis comprising a corn beard extract or a fraction thereof A method of treating atopic dermatitis comprising the step of, a food composition for improving atopic dermatitis comprising a corn beard extract or a fraction thereof, a quasi-drug composition for preventing or improving atopic dermatitis comprising a corn beard extract or a fraction thereof, and a corn beard extract or It relates to a cosmetic composition for preventing or improving atopic dermatitis comprising a fraction thereof.
옥수수(Zea mays L.)수염은 옥수수의 부산물로 열매를 싸고 있는 실 같은 부분으로 옥미발, 옥촉서예 등으로 불린다. 이러한 옥수수수염에는 지방유, 지방, 쓴맛 글리코사이드, 사포닌, 알칼로이드, 메이신 외에 이노시톨, 크립토잔틴, 판토텐산, 비타민 C, 말산, 타타릭산, 글루코스, 자일란 등이 함유되어있으며, 특히 다량의 비타민 K가 포함되어 있다. 또한, 옥수수수염에 함유된 성분 중 하나인 플라보노이드 계열로 메이신(maysin), 아피메이신(apimaysin), 메록시메이신(methoxymaysin)이 있으며 이 중 메이신은 옥수수수염에 가장 많이 함유되어 있는 대표적인 물질이며, 이러한 메이신은 corn earworm의 생육 억제활성, 종양 세포주에 대한 세포독성 효과 및 라디컬 소거활성 등이 보고되어 있다. 최근에는 옥수수수염 추출물이 산화방지 활성 및 UV로부터 피부 보호효과가 있다는 연구가 발표 되었으며, 옥수수수염으로부터 유효성분인 메이신 및 유사물질을 다량 추출하는 방법에 대한 연구결과도 보고되었다.Corn ( Zea mays L.) is a by-product of corn, which is the thread-like part that wraps the fruit and is called jade mibal and jade calligraphy. These corn beards contain fatty oils, fats, bitter glycosides, saponins, alkaloids, and macin, as well as inositol, cryptoxanthine, pantothenic acid, vitamin C, malic acid, tartaric acid, glucose, xylan, etc., and in particular, a large amount of vitamin K is included. Has been. In addition, there are maysin, apimaysin, and methoxymaysin as the flavonoids, one of the ingredients contained in corn beard. In addition, this mecine has been reported to inhibit the growth of corn earworm, cytotoxic effect on tumor cell lines, and radical scavenging activity. Recently, studies have been published that corn beard extract has antioxidant activity and skin protection effect from UV, and research results on a method of extracting large amounts of the active ingredients, mayine and similar substances from corn beard, have also been reported.
피부는 다양한 환경적인 요인에 대해 신체를 보호하는 물리적 장벽으로서 기능을 갖는 가장 첫 번째 기관이며, 다양한 환경적인 자극은 면역계의 활성화를 일으킨다. 또한, 피부는 다양한 피부 질환중 하나인 아토피성 피부염은 일반적으로 유아 및 소아에게 발생하는 만성 및 재발성 피부질환으로 심한 가려움과 피부습진 등의 증상이 여러 가지 원인에 의해 악화, 완화, 재발이 계속된다. 산업화된 나라에서 아토피 피부염 발생률은 계속하여 증가되고 있는 실정이며 성인의 1-5%, 영유아 및 어린이의 10-20%에 이르고 있어, 이를 해결하기 위한 연구가 세계적으로 활발히 진행되고 있다. The skin is the first organ to function as a physical barrier that protects the body against various environmental factors, and various environmental stimuli trigger the activation of the immune system. In addition, atopic dermatitis, one of various skin diseases of the skin, is a chronic and recurrent skin disease that generally occurs in infants and children. Symptoms such as severe itching and skin eczema continue to worsen, relieve, and recur due to various causes. do. In industrialized countries, the incidence of atopic dermatitis continues to increase, reaching 1-5% of adults and 10-20% of infants and children, and research to solve this problem is being actively conducted worldwide.
이에 따라, 면역조절 물질, 항염증효과를 나타내는 물질, 아토피 유발 신호전달 억제물질 등과 같은 다양한 성분을 이용하여, 아토피 치료효과를 나타내는 제제를 개발하고 있고, 특히 항염증 효과가 우수한 비스테로이드 계통 및 스테로이드 계통의 물질을 대상으로 활발한 연구가 진행되고 있으나, 이들의 제조단가가 높고, 아토피 치료효과가 일회성이며, 부작용이 검증되지 않았거나 심각한 부작용을 나타낸다는 등의 다양한 원인으로 인하여, 아토피 치료제가 상용화되지 못하고 있는 실정이다. Accordingly, by using various components such as immunomodulatory substances, substances exhibiting anti-inflammatory effects, substances that inhibit atopy-inducing signal transduction, etc., formulations exhibiting atopic treatment effects are being developed. In particular, nonsteroidal systems and steroids with excellent anti-inflammatory effects Active research is being conducted on substances of the system, but due to various causes, such as high manufacturing cost, atopic treatment effect, and side effects not verified or serious side effects, atopic treatments have not been commercialized. It is not possible.
한편에서는, 이러한 단점을 해결하기 위하여, 부작용을 나타내지 않는 것으로 확인된 천연물을 대상으로 하여 아토피 치료효과를 나타내는 생약제제를 개발하려는 연구가 활발히 진행되고 있다. 예를 들어, 한국등록특허 제1528135호에는 백장미 꽃잎 추출물 또는 이로부터 분리된 피로갈롤 화합물을 유효성분으로 포함하는 아토피성 피부염 예방 또는 치료용 약제학적 조성물이 개시되어 있고, 한국등록특허 제1698869호에는 오배자, 지부자, 사상자, 어성초, 형개, 고삼, 대황, 자초, 가자 및 천화분을 포함하는 한약재로부터 추출된 추출물을 유효성분으로 포함하는 아토피 피부염 예방 또는 치료용 조성물이 개시되어 있으며, 한국등록특허 제1814389호에는 번행초 추출물을 포함하고 항산화활성, 항염증 및 아토피 유발 억제 효능을 가지는 화장료 조성물이 개시되어 있고, 한국등록특허 제1828204호에는 산수유 추출물, 찔레 추출물, 측백 추출물, 싸리나무 추출물, 및 율엽 추출물을 포함하는 항아토피 조성물이 개시되어 있다. 그러나, 이들 천연물 연구를 통해 얻어진 결과물은 우수한 안전성을 나타내는 반면, 아토피를 치료하기 위하여 장기간의 치료시간이 필요하다는 단점이 있었다.On the other hand, in order to solve these shortcomings, research is being actively conducted to develop a herbal preparation that exhibits atopic therapeutic effect targeting natural products that have not been found to exhibit side effects. For example, Korean Patent No. 1528135 discloses a pharmaceutical composition for the prevention or treatment of atopic dermatitis comprising an extract of white rose petals or a pyrogallol compound isolated therefrom as an active ingredient. A composition for preventing or treating atopic dermatitis comprising an extract extracted from herbal medicinal herbs including Baeja Oh, Jibuja, Casualty, Eoseongcho, Hyeonggae, Gosam, Rhubarb, Jacho, Gaja, and Cheonhwabun as an active ingredient is disclosed, and Korean Patent No. 1814389 No. 1 discloses a cosmetic composition comprising a Bunhaengcho extract and having antioxidant activity, anti-inflammatory and atopic-inducing inhibitory effects, and Korean Patent No. 1828204 discloses cornus milk extract, brier extract, cypress extract, cypress extract, and Yule leaf extract. An anti-atopic composition comprising is disclosed. However, while the results obtained through these natural product studies show excellent safety, there is a disadvantage that a long treatment time is required to treat atopy.
이러한 배경하에서, 본 발명자들은 안전하면서도 보다 효과적으로 아토피 피부염을 치료하는 효과를 나타낼 수 있는 제제를 개발하고자 예의 연구노력한 결과, 옥수수수염 추출물이 효과적으로 아토피 피부염을 치료할 수 있음을 확인하고, 본 발명을 완성하였다.Under this background, the present inventors have made extensive research efforts to develop a formulation that can safely and more effectively treat atopic dermatitis, and as a result, it has been confirmed that corn beard extract can effectively treat atopic dermatitis, and has completed the present invention. .
본 발명의 하나의 목적은 옥수수수염 추출물 또는 그의 분획물을 포함하는 아토피 피부염 예방 또는 치료용 약학 조성물을 제공하는 것이다.One object of the present invention is to provide a pharmaceutical composition for preventing or treating atopic dermatitis, comprising a corn beard extract or a fraction thereof.
본 발명의 다른 하나의 목적은 상기 약학 조성물을 인간을 제외한 아토피 피부염 의심 개체에 투여하는 단계를 포함하는 아토피 피부염의 치료방법을 제공하는 것이다.Another object of the present invention is to provide a method for treating atopic dermatitis comprising administering the pharmaceutical composition to a suspected subject of atopic dermatitis except for humans.
본 발명의 또 다른 하나의 목적은 옥수수수염 추출물 또는 이의 분획물을 포함하는 아토피 피부염 개선용 식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a food composition for improving atopic dermatitis comprising a corn beard extract or a fraction thereof.
본 발명의 또 다른 하나의 목적은 옥수수수염 추출물 또는 이의 분획물을 포함하는 아토피 피부염의 예방 또는 개선용 의약외품 조성물을 제공하는 것이다.Another object of the present invention is to provide a quasi-drug composition for preventing or improving atopic dermatitis comprising a corn beard extract or a fraction thereof.
본 발명의 또 다른 하나의 목적은 옥수수수염 추출물 또는 이의 분획물을 포함하는 아토피 피부염의 예방 또는 개선용 화장료 조성물을 제공하는 것이다.Another object of the present invention is to provide a cosmetic composition for preventing or improving atopic dermatitis comprising a corn beard extract or a fraction thereof.
본 발명자들은 안전하면서도 보다 효과적으로 아토피 피부염을 치료하는 효과를 나타낼 수 있는 제제를 개발하고자, 안전성이 입증된 천연물을 대상으로 연구를 수행한 결과, 옥수수수염에 주목하게 되었다. The present inventors have conducted research on natural products with proven safety in order to develop a formulation that can exhibit the effect of treating atopic dermatitis more effectively while being safe, and as a result, attention has been paid to corn beard.
상기 옥수수수염을 에탄올로 추출하여 수득한 옥수수수염 추출물이 염증성 질환에 유효한 효과를 나타내는지의 여부를 확인하기 위하여, LPS 처리된 대식세포에 처리한 결과, 상기 대식세포에서 LPS 자극에 의해 생성량이 증가되는 NO(nitric oxide) 및 TNF-α(tumor necrosis factor-α)의 수준을 옥수수수염 추출물이 감소시키는 효과를 나타냄을 확인하였다. 이에, 상기 옥수수수염 추출물이 아토피 피부염에 대하여도 유효한 효과를 나타내는지를 확인하고자 하였다. 즉, IFN-γ 및 TNF-α로 자극된 상피세포에서는 염증성 사이토카인의 일종인 TARC(thymus and activation regualted chemokine)의 생성량이 증가되는데, 이러한 염증성 사이토카인의 생성량 증가는 아토피 피부염의 발병원인 중의 하나로 알려져 있다. 상기 IFN-γ 및 TNF-α로 자극된 상피세포에 옥수수수염 추출물을 처리한 결과, TARC의 생성량이 감소됨을 확인하였다. 결국, 본 발명에서 제공하는 옥수수수염 추출물은 염증을 억제할 뿐만 아니라, 아토피 피부염의 원인증상을 억제할 수 있으므로, 아토피 피부염의 예방 또는 치료에 유효한 효과를 나타냄을 알 수 있었다.In order to check whether the corn beard extract obtained by extracting the corn beard with ethanol exhibits an effective effect on inflammatory diseases, as a result of treatment on LPS-treated macrophages, the amount of production increased by LPS stimulation in the macrophages. It was confirmed that the level of NO (nitric oxide) and TNF-α (tumor necrosis factor-α) was reduced by the corn beard extract. Accordingly, it was attempted to confirm whether the corn beard extract exhibited an effective effect against atopic dermatitis. That is, in epithelial cells stimulated with IFN-γ and TNF-α, the production of TARC (thymus and activation regualted chemokine), a type of inflammatory cytokine, is increased, and this increase in the production of inflammatory cytokines is one of the causes of atopic dermatitis. Is known. The IFN-γ and TNF-α-stimulated epithelial cells were treated with corn beard extract, and as a result, it was confirmed that the amount of TARC produced was reduced. As a result, it was found that the corn beard extract provided by the present invention not only suppresses inflammation, but also suppresses the causative symptoms of atopic dermatitis, thus exhibiting an effective effect in the prevention or treatment of atopic dermatitis.
이처럼, 상기 옥수수수염 추출물이 아토피 피부염에 대하여 치료효과를 나타냄은 이전에 알려진 바 없었으며, 본 발명자들에 의하여 처음으로 규명되었다.As such, it has not been known before that the corn beard extract exhibits a therapeutic effect on atopic dermatitis, and was first identified by the present inventors.
상술한 목적을 달성하기 위한 본 발명의 일 실시양태는 옥수수수염 추출물 또는 이의 분획물을 포함하는 아토피 피부염의 예방 또는 치료용 약학 조성물을 제공한다.One embodiment of the present invention for achieving the above object provides a pharmaceutical composition for the prevention or treatment of atopic dermatitis comprising a corn beard extract or a fraction thereof.
본 발명의 용어, "옥수수수염(corn silk)"이란, 옥미발, 옥촉서예 등으로 호칭되고, 옥수수의 열매를 싸고 있는 실 같은 부분을 의미한다. 상기 옥수수수염에는 지방유, 지방, 쓴맛 글리코사이드, 사포닌, 알칼로이드, 메이신 외에 이노시톨, 크립토잔틴, 판토텐산, 비타민 C, 말산, 타타릭산, 글루코스, 자일란 등이 함유되어있으며, 특히 다량의 비타민 K가 포함되어 있다고 알려져 있다(Cha SM, et al., Effect of particle size on physico-chemical properties and antioxidant activity of corn silk powder. Korean J. Crop Sci. 57: 41-50 (2012)). 또한, 옥수수수염에 함유된 성분 중 하나인 플라보노이드 계열로 메이신(maysin), 아피메이신(apimaysin), 메록시메이신(methoxymaysin)이 있으며 이 중 메이신은 옥수수수염에 가장 많이 함유되어 있는 대표적인 물질이며, 이러한 메이신은 종양 세포주에 대한 세포독성 효과 및 라디컬 소거활성 등을 나타낸다고 알려져 있다(Ku KM, et al., Antioxidant activity and functional components of corn silk (Zea mays L.). Korean J. Plant Res. 22: 323-329 (2009)). The term "corn silk" of the present invention is called jade mibal, jade calligraphy, etc., and means a thread-like part that wraps the fruit of corn. In addition to fatty oils, fats, bitter glycosides, saponins, alkaloids, and macin, the corn beard contains inositol, cryptoxanthine, pantothenic acid, vitamin C, malic acid, tartaric acid, glucose, xylan, etc., and in particular, a large amount of vitamin K is included. (Cha SM, et al., Effect of particle size on physico-chemical properties and antioxidant activity of corn silk powder. Korean J. Crop Sci. 57: 41-50 (2012)). In addition, there are maysin, apimaysin, and methoxymaysin as the flavonoids, which are one of the ingredients contained in corn beard, of which maysin is the most common substance contained in corn beard. It is known that this mecine exhibits cytotoxic effects and radical scavenging activity against tumor cell lines (Ku KM, et al., Antioxidant activity and functional components of corn silk (Zea mays L.). Korean J. Plant Res. 22: 323-329 (2009)).
본 발명에 있어서, 상기 옥수수수염은 상업적으로 판매되는 것을 구입하여 사용하거나, 자연에서 채취 또는 재배된 것을 사용할 수 있으나, 이에 제한되지 않는다.In the present invention, the corn beard may be used by purchasing commercially sold ones, or those harvested or grown in nature, but is not limited thereto.
본 발명의 용어, "추출물"이란, 옥수수수염을 추출 처리하여 얻어지는 추출액, 상기 추출액의 희석액이나 농축액, 상기 추출액을 건조하여 얻어지는 건조물, 상기 추출액의 조정제물이나 정제물, 또는 이들의 혼합물 등, 추출액 자체 및 추출액을 이용하여 형성 가능한 모든 제형의 추출물을 포함한다. In terms of the present invention, the term "extract" refers to an extract obtained by extracting corn beard, a dilution or concentrate of the extract, a dried product obtained by drying the extract, a crude or purified product of the extract, or a mixture thereof, etc. It includes extracts of all formulations that can be formed using itself and extracts.
본 발명에 있어서, 상기 상기 옥수수수염 추출물은 "NICS-1" 또는 "NICS-3"과 혼용되어 명명될 수 있다.In the present invention, the corn beard extract may be named "NICS-1" or "NICS-3" interchangeably.
본 발명의 옥수수수염 추출물에 있어서, 상기 혼합물을 추출하는 방법은 특별히 제한되지 않으며, 당해 기술 분야에서 통상적으로 사용하는 방법에 따라 추출할 수 있다. 상기 추출 방법의 비제한적인 예로는, 열수 추출법, 초음파 추출법, 여과법, 환류 추출법 등을 들 수 있으며, 이들은 단독으로 수행되거나 2종 이상의 방법을 병용하여 수행될 수 있다.In the corn beard extract of the present invention, a method of extracting the mixture is not particularly limited, and may be extracted according to a method commonly used in the art. Non-limiting examples of the extraction method include a hot water extraction method, an ultrasonic extraction method, a filtration method, a reflux extraction method, and the like, and these may be performed alone or in combination of two or more methods.
본 발명에서 상기 추출에 사용되는 용매의 종류는 특별히 제한되지 않으며, 당해 기술 분야에서 공지된 임의의 용매를 사용할 수 있다. 상기 추출 용매의 비제한적인 예로는 물, 알코올 또는 이들의 혼합 용매 등을 들 수 있고, 이들은 단독으로 사용되거나 1종 이상 혼합하여 사용될 수 있으며, 구체적으로 물이 사용될 수 있다. 알코올을 용매로 사용하는 경우에는 구체적으로 탄소수 1 내지 4의 알코올을 사용할 수 있다.In the present invention, the type of solvent used for the extraction is not particularly limited, and any solvent known in the art may be used. Non-limiting examples of the extraction solvent may include water, alcohol, or a mixed solvent thereof, and these may be used alone or in combination of one or more, and specifically water may be used. When alcohol is used as a solvent, an alcohol having 1 to 4 carbon atoms may be specifically used.
본 발명의 용어, "분획물"은 여러 다양한 구성 성분들을 포함하는 혼합물로부터 특정 성분 또는 특정 성분 그룹을 분리하기 위하여 분획을 수행하여 얻어진 결과물을 의미한다.As used herein, the term "fraction" means a result obtained by performing fractionation in order to separate a specific component or a specific group of components from a mixture containing several different constituents.
본 발명에서 상기 분획물을 얻는 분획 방법은 특별히 제한되지 않으며, 당해 기술 분야에서 통상적으로 사용하는 방법에 따라 수행될 수 있다. 상기 분획 방법의 비제한적인 예로는, 다양한 용매를 처리하여 수행하는 용매 분획법, 일정한 분자량 컷-오프 값을 갖는 한외 여과막을 통과시켜 수행하는 한외여과 분획법, 다양한 크로마토그래피(크기, 전하, 소수성 또는 친화성에 따른 분리를 위해 제작된 것)를 수행하는 크로마토그래피 분획법, 및 이들의 조합 등이 있다. 구체적으로, 본 발명의 옥수수수염을 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 performed according to a method commonly used in the art. Non-limiting examples of the fractionation method include a solvent fractionation method performed by treating various solvents, an ultrafiltration fractionation method performed by passing an ultrafiltration membrane having a constant molecular weight cut-off value, and various chromatography (size, charge, hydrophobicity). Or a chromatographic fractionation method for performing separation according to affinity), and combinations thereof. Specifically, there may be mentioned a method of obtaining a fraction from the extract by treating the extract obtained by extracting the corn beard of the present invention with a predetermined solvent.
본 발명에서 상기 분획물을 얻는 데 사용되는 분획 용매의 종류는 특별히 제한되지 않으며, 당해 기술 분야에서 공지된 임의의 용매를 사용할 수 있다. 상기 분획 용매의 비제한적인 예로는 물, 탄소수 1 내지 4의 알코올 등의 극성 용매; 헥산(Hexan), 에틸 아세테이트(Ethyl acetate), 클로로포름(Chloroform), 디클로로메탄(Dichloromethane) 등의 비극성 용매; 또는 이들의 혼합용매 등을 들 수 있다. 이들은 단독으로 사용되거나 1종 이상 혼합하여 사용될 수 있지만, 이에 제한되는 것은 아니다.In the present invention, the type of fractionation solvent used to obtain the fraction is not particularly limited, and any solvent known in the art may be used. Non-limiting examples of the fractionation solvent include polar solvents such as water and alcohols having 1 to 4 carbon atoms; Non-polar solvents such as hexane, ethyl acetate, chloroform, and dichloromethane; Or a mixed solvent of these, etc. are mentioned. These may be used alone or in combination of one or more, but are not limited thereto.
또한, 상기 추출물 또는 분획물은 추출 후 건조 분말 형태로 제조되어 사용될 수 있지만, 이제 제한되는 것은 아니다.In addition, the extract or fraction may be prepared and used in a dry powder form after extraction, but is not limited thereto.
본 발명의 용어, "아토피 피부염(Atopic dermatitis; AD)"이란, 자가면역 피부질환의 일종으로서, 피부의 부스럼, 습진, 간지러움을 동반하는 피부질환을 의미한다. 상기 아토피 피부염의 발병에는 환경적 요인 및 유전학적 요인 모두가 관여하는 것으로 알려져 있으나, 정확한 발병기전은 규명되지 않았다. 본 발명에서, 상기 아토피 피부염은 "AD"와 혼용되어 명명될 수 있다.The term of the present invention, "Atopic dermatitis (AD)" is a kind of autoimmune skin disease, and refers to a skin disease accompanied by skin swelling, eczema, and itching. It is known that both environmental and genetic factors are involved in the onset of atopic dermatitis, but the exact pathogenesis has not been identified. In the present invention, the atopic dermatitis may be named interchangeably with "AD".
본 발명의 용어, "예방"은 상기 추출물을 포함하는 조성물의 투여로 아토피 피부염을 억제 또는 지연시키는 모든 행위를 의미한다. The term "prevention" of the present invention means any action of suppressing or delaying atopic dermatitis by administration of a composition comprising the extract.
본 발명의 용어, "치료"는 상기 추출물을 포함하는 조성물의 투여로 아토피 피부염의 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다.The term "treatment" of the present invention refers to any action in which symptoms of atopic dermatitis are improved or advantageously changed by administration of a composition comprising the extract.
본 발명의 일 실시예에 의하면, 본 발명의 옥수수수염 추출물(NICS-1 및 NICS-3)은 대식세포(RAW 264.7 세포)와 상피세포(HaCaT 세포)에서 세포독성을 나타내지 않았고, 대식세포(RAW 264.7 세포)에 처리할 경우 LPS 자극에 의한 NO 생성에 미치는 영향을 분석한 결과, LPS 단독 처리구에서 NO생성량이 무처리 군에 비해서 크게 증가하였으나, 옥수수염 추출물(NICS-1 및 NICS-3)을 처리한 군에서는 농도 의존적으로 NO생성량이 감소함을 확인하였다(도 1). 또한, LPS로 자극된 대식세포(RAW 264.7 세포)에서 생성되는 TNF-α 생성량을 기준으로 본 발명의 옥수수수염 추출물(NICS-1 및 NICS-3)의 효과를 분석한 결과, 옥수수수염 추출물(NICS-1 및 NICS-3)이 RAW 264.7 세포에서 TNF-α 분비를 억제함을 확인하였다(도 2). 끝으로, 상기 옥수수수염 추출물(NICS-1 및 NICS-3)은 상피세포인 HaCaT 세포에서 TARC 생성을 억제하는 효과를 나타냄을 확인하였다(도 3).According to an embodiment of the present invention, corn beard extracts (NICS-1 and NICS-3) of the present invention did not show cytotoxicity in macrophages (RAW 264.7 cells) and epithelial cells (HaCaT cells), and macrophages (RAW 264.7 cells), as a result of analyzing the effect of LPS stimulation on the production of NO by LPS stimulation, the amount of NO production in the LPS alone treatment increased significantly compared to the untreated group, but corn salt extracts (NICS-1 and NICS-3) were used. In the treated group, it was confirmed that the amount of NO production decreased in a concentration-dependent manner (FIG. 1). In addition, as a result of analyzing the effect of the corn beard extract (NICS-1 and NICS-3) of the present invention based on the amount of TNF-α produced in LPS-stimulated macrophages (RAW 264.7 cells), corn beard extract (NICS -1 and NICS-3) were confirmed to inhibit the secretion of TNF-α in RAW 264.7 cells (Fig. 2). Finally, it was confirmed that the corn beard extract (NICS-1 and NICS-3) exhibited an effect of inhibiting TARC production in HaCaT cells, which are epithelial cells (FIG. 3).
상피세포에서 과다하게 생성되는 염증성 사이토카인은 아토피 피부염의 발병원인 중의 하나로 알려져 있으므로, 상기 결과로부터 본 발명의 옥수수수염 추출물이 아토피 피부염의 예방 또는 치료효과를 나타냄을 알 수 있었다.Since inflammatory cytokines generated excessively in epithelial cells are known as one of the causes of atopic dermatitis, from the above results, it was found that the corn beard extract of the present invention exhibits a preventive or therapeutic effect of atopic dermatitis.
본 발명의 약학 조성물은 조성물 총 중량에 대하여 상기 추출물을 0.001 내지 80, 구체적으로 0.001 내지 70, 더욱 구체적으로 0.001 내지 60 중량%로 포함할 수 있으나, 이에 제한되지 않는다.The pharmaceutical composition of the present invention may include 0.001 to 80, specifically 0.001 to 70, more specifically 0.001 to 60% by weight of the extract based on the total weight of the composition, but is not limited thereto.
또한, 상기 약학 조성물은 약학 조성물의 제조에 통상적으로 사용하는 약학적으로 허용가능한 담체, 부형제 또는 희석제를 추가로 포함할 수 있고, 상기 담체는 비자연적 담체(non-naturally occuring carrier)를 포함할 수 있다. 상기 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 addition, the pharmaceutical composition may further include a pharmaceutically acceptable carrier, excipient, or diluent commonly used in the manufacture of pharmaceutical compositions, and the carrier may include a non-naturally occurring carrier. have. Examples of the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline Cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oils.
또한, 상기 약학 조성물은 각각 통상의 방법에 따라 정제, 환제, 산제, 과립제, 캡슐제, 현탁제, 내용액제, 유제, 시럽제, 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 경피흡수제, 겔제, 로션제, 연고제, 크림제, 첩부제, 카타플라스마제, 페이스트제, 스프레이, 피부 유화액, 피부 현탁액, 경피 전달성 패치, 약물 함유 붕대 또는 좌제의 형태로 제형화하여 사용할 수 있다. 구체적으로, 제형화할 경우 통상 사용하는 충진제, 중량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. 경구투여를 위한 고형제제로는 정제, 환제, 산제, 과립제, 캡슐제 등을 포함하지만, 이에 제한되지 않는다. 이러한 고형제제는 적어도 하나 이상의 부형제, 예를 들면, 전분, 칼슘 카보네이트, 수크로오스, 락토오스, 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제 등도 사용될 수 있다. 경구를 위한 액상물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등을 첨가하여 조제될 수 있다. 비경구 투여를 위한 제제는 멸균된 수용액, 비수성 용제, 현탁제, 유제, 동결건조 제제 및 좌제를 포함한다. 비수성 용제 및 현탁제로는 프로필렌 글리콜, 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 오일, 에틸올레이트와 같은 주사가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔, 마크로골, 트윈 61, 카카오지, 라우린지, 글리세로젤라틴 등이 사용될 수 있다.In addition, the pharmaceutical compositions are each tablet, pill, powder, granule, capsule, suspension, solution, emulsion, syrup, sterilized aqueous solution, non-aqueous solvent, suspension, emulsion, freeze-dried, transdermal, respectively, according to a conventional method. It can be formulated and used in the form of absorbents, gels, lotions, ointments, creams, patches, cataplasmas, pastes, sprays, skin emulsions, skin suspensions, transdermal delivery patches, drug-containing bandages or suppositories. Specifically, when formulated, it may be prepared using diluents or excipients such as fillers, weight agents, binders, wetting agents, disintegrants, surfactants, etc. that are commonly used. Solid preparations for oral administration include, but are not limited to, tablets, pills, powders, granules, capsules, and the like. These solid preparations may be prepared by mixing at least one or more excipients, for example starch, calcium carbonate, sucrose, lactose, gelatin, and the like. In addition, in addition to simple excipients, lubricants such as magnesium stearate and talc may be used. It can be prepared by adding various excipients, such as wetting agents, sweetening agents, fragrances, preservatives, and the like, in addition to oral liquids and liquid paraffin. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations, and suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyloleate, and the like may be used. As a base for suppositories, Witepsol, Macrogol, Tween 61, cacao butter, laurin paper, glycerogelatin, and the like can be used.
본 발명의 다른 실시양태는 상기 약학 조성물을 인간을 제외한 아토피 피부염 의심 개체에 투여하는 단계를 포함하는 아토피 피부염의 치료방법을 제공한다.Another embodiment of the present invention provides a method for treating atopic dermatitis, comprising administering the pharmaceutical composition to a suspected individual of atopic dermatitis other than humans.
본 발명의 용어, "투여"는 적절한 방법으로 개체에게 상기 추출물을 포함하는 조성물을 도입하는 행위를 의미한다.The term "administration" of the present invention refers to the act of introducing a composition comprising the extract to an individual by an appropriate method.
본 발명의 용어, "개체"는 아토피 피부염이 발병하였거나 발병할 수 있는 인간을 포함한 쥐, 생쥐, 가축 등의 모든 동물을 의미한다. 구체적인 예로, 인간을 포함한 포유동물일 수 있다.As used herein, the term "individual" refers to all animals such as rats, mice, and livestock, including humans who have or may develop atopic dermatitis. As a specific example, it may be a mammal including a human.
본 발명의 약학 조성물은 약학적으로 유효한 양으로 투여한다. 상기 용어, "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효 용량 수준은 개체 종류 및 중증도, 연령, 성별, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료 기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 예를 들면, 상기 옥수수수염 추출물은 1일 0.01 내지 500 mg/kg으로, 구체적으로 10 내지 100 mg/kg의 용량으로 투여할 수 있으며, 상기 투여는 하루에 한 번 또는 수회 나누어 투여할 수도 있다. The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. The term "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is the type and severity of the subject, age, sex, activity of the drug, Sensitivity to drugs, time of administration, route of administration and rate of excretion, duration of treatment, factors including drugs used concurrently, and other factors well known in the medical field. For example, the corn beard extract may be administered at a dose of 0.01 to 500 mg/kg per day, specifically 10 to 100 mg/kg, and the administration may be administered once or several times a day.
상기 약학 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와는 순차적 또는 동시에 투여될 수 있다. 그리고 단일 또는 다중 투여될 수 있다. 상기 요소를 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 당업자에 의해 용이하게 결정될 수 있다.The pharmaceutical composition may be administered as an individual therapeutic agent or administered in combination with other therapeutic agents, and may be administered sequentially or simultaneously with a conventional therapeutic agent. And can be administered single or multiple. It is important to administer an amount capable of obtaining the maximum effect in a minimum amount without side effects in consideration of all the above factors, and can be easily determined by a person skilled in the art.
또한, 상기 약학 조성물은 목적하는 방법에 따라 경구 투여하거나 비경구 투여(예를 들어, 정맥 내, 피하, 복강 내 또는 국소에 적용)할 수 있으며, 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 시간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다.In addition, the pharmaceutical composition may be administered orally or parenterally (for example, intravenous, subcutaneous, intraperitoneal or topical application) according to a desired method, and the dosage may be the patient's condition and weight, the degree of disease , It depends on the drug form, administration route and time, but may be appropriately selected by those skilled in the art.
본 발명의 또 다른 실시양태는 옥수수수염 추출물 또는 이의 분획물을 포함하는 아토피 피부염 개선용 식품 조성물을 제공한다.Another embodiment of the present invention provides a food composition for improving atopic dermatitis comprising a corn beard extract or a fraction thereof.
이때, 상기 옥수수수염, 추출물, 분획물 및 아토피 피부염의 정의는 상기에서 설명한 바와 같다.At this time, the definition of the corn beard, extract, fraction, and atopic dermatitis are as described above.
본 발명의 용어, "개선"은 상기 추출물을 포함하는 조성물의 투여로 치료되는 상태와 관련된 파라미터, 예를 들면 증상의 정도를 적어도 감소시키는 모든 행위를 의미한다.The term "improvement" of the present invention means any action of at least reducing the severity of a parameter, such as a symptom, related to the condition to be treated by administration of a composition comprising the extract.
본 발명의 용어, "식품"은 육류, 소시지, 빵, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알코올음료, 비타민 복합제, 건강 기능 식품 및 건강 식품 등이 있으며, 통상적인 의미에서의 식품을 모두 포함한다.As used herein, the term "food" refers to meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages , Vitamin complexes, health functional foods and health foods, and all foods in the usual sense are included.
본 발명의 식품 조성물은 일상적으로 섭취가능한 옥수수수염으로부터 유래되었기 때문에 높은 아토피 피부염 개선 효과를 기대할 수 있으므로, 건강 증진 목적으로 매우 유용하게 사용될 수 있다.Since the food composition of the present invention is derived from corn beard that can be consumed on a daily basis, a high atopic dermatitis improvement effect can be expected, and thus it can be very usefully used for health promotion purposes.
상기 건강 기능(성) 식품(functional food)이란, 특정보건용 식품(food for special health use, FoSHU)과 동일한 용어로, 영양 공급 외에도 생체조절기능이 효율적으로 나타나도록 가공된 의학, 의료효과가 높은 식품을 의미한다. 여기서 '기능(성)'이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건용도에 유용한 효과를 얻는 것을 의미한다. 본 발명의 식품은 당 업계에서 통상적으로 사용되는 방법에 의하여 제조가능하며, 상기 제조시에는 당 업계에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 또한, 상기 식품의 제형은 식품으로 인정되는 제형이면 제한없이 제조될 수 있다. The health function (functional food) is the same term as food for special health use (FoSHU).In addition to nutritional supply, the term "functional food" refers to medicine that is processed so that the bioregulatory function is effectively displayed. Means food. Here, the term'function (sex)' means to control nutrients for the structure and function of the human body or to obtain useful effects for health purposes such as physiological actions. The food of the present invention can be prepared by a method commonly used in the art, and during the production, raw materials and ingredients commonly added in the art may be added to prepare the food product. In addition, the formulation of the food may be prepared without limitation as long as it is a formulation recognized as a food.
본 발명의 식품용 조성물은 다양한 형태의 제형으로 제조될 수 있으며, 일반 약품과는 달리 천연물을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고, 휴대성이 뛰어나므로, 본 발명의 식품은 아토피 피부염의 개선 효과를 증진시키기 위한 보조제로 섭취가 가능하다.The food composition of the present invention can be prepared in various forms, and unlike general drugs, it has the advantage of not having side effects that may occur when taking drugs for a long time using natural substances as raw materials, and is excellent in portability. The food of the present invention can be ingested as an adjuvant for enhancing the effect of improving atopic dermatitis.
상기 건강 식품(health food)은 일반식품에 비해 적극적인 건강유지나 증진 효과를 가지는 식품을 의미하고, 건강보조식품(health supplement food)은 건강보조 목적의 식품을 의미한다. 경우에 따라, 건강 기능 식품, 건강식품, 건강보조식품의 용어는 호용된다.The health food refers to a food having an active health maintenance or promotion effect compared to a general food, and a health supplement food refers to a food for health supplement purposes. In some cases, the terms health functional food, health food, and health supplement are used interchangeably.
구체적으로, 상기 건강 기능 식품은 본 발명의 화합물을 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 compound of the present invention to food materials such as beverages, teas, spices, gums, confectionery, or encapsulating, powdering, and suspending. It means bringing about an effect, but unlike general drugs, it has the advantage of having no side effects that may occur when taking the drug for a long time by using food as a raw material.
상기 식품 조성물은 생리학적으로 허용 가능한 담체를 추가로 포함할 수 있는데, 담체의 종류는 특별히 제한되지 않으며 당해 기술 분야에서 통상적으로 사용되는 담체라면 어느 것이든 사용할 수 있다.The food composition may further include a physiologically acceptable carrier, and the kind of carrier is not particularly limited, and any carrier commonly used in the art may be used.
또한, 상기 식품 조성물은 식품 조성물에 통상 사용되어 냄새, 맛, 시각 등을 향상시킬 수 있는 추가 성분을 포함할 수 있다. 예들 들어, 비타민 A, C, D, E, B1, B2, B6, B12, 니아신(niacin), 비오틴(biotin), 폴레이트(folate), 판토텐산(panthotenic acid) 등을 포함할 수 있다. 또한, 아연(Zn), 철(Fe), 칼슘(Ca), 크롬(Cr), 마그네슘(Mg), 망간(Mn), 구리(Cu), 크륨(Cr) 등의 미네랄; 및 라이신, 트립토판, 시스테인, 발린 등의 아미노산을 포함할 수 있다. In addition, the food composition may include additional ingredients that are commonly used in food compositions to improve smell, taste, vision, and the like. For example, vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, panthotenic acid, and the like may be included. In addition, minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu), and chromium (Cr); And amino acids such as lysine, tryptophan, cysteine, and valine.
또한, 상기 식품 조성물은 방부제(소르빈산 칼륨, 벤조산나트륨, 살리실산, 데히드로초산나트륨 등), 살균제(표백분과 고도 표백분, 차아염소산나트륨 등), 산화방지제(부틸히드록시아니졸(BHA), 부틸히드록시톨류엔(BHT) 등), 착색제(타르색소 등), 발색제(아질산 나트륨, 아초산 나트륨 등), 표백제(아황산나트륨), 조미료(MSG 글루타민산나트륨 등), 감미료(둘신, 사이클레메이트, 사카린, 나트륨 등), 향료(바닐린, 락톤류 등), 팽창제(명반, D-주석산수소칼륨 등), 강화제, 유화제, 증점제(호료), 피막제, 검기초제, 거품억제제, 용제, 개량제 등의 식품 첨가물(food additives)을 포함할 수 있다. 상기 첨가물은 식품의 종류에 따라 선별되고 적절한 양으로 사용될 수 있다.In addition, the food composition includes preservatives (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate, etc.), disinfectants (bleaching and highly bleaching, sodium hypochlorite, etc.), antioxidants (butylhydroxyanisole (BHA), butylhydride, etc.) Oxytoleuene (BHT), etc.), coloring agent (tar color, etc.), coloring agent (sodium nitrite, sodium nitrite, etc.), bleach (sodium sulfite), seasoning (MSG sodium glutamate, etc.), sweetener (dulsin, cyclamate, saccharin, etc.) , Sodium, etc.), flavorings (vanillin, lactones, etc.), expanding agents (alum, D-potassium hydrogen stannate, etc.), reinforcing agents, emulsifying agents, thickening agents (thickening agents), coating agents, gum base agents, foam inhibitors, solvents, improving agents, etc. It may contain food additives. The additive may be selected according to the type of food and used in an appropriate amount.
본 발명의 식품 조성물의 일 예로 건강음료 조성물로 사용될 수 있으며, 이 경우 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드; 말토스, 슈크로스와 같은 디사카라이드; 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드; 자일리톨, 소르비톨, 에리트리톨 등의 당알콜일 수 있다. 감미제는 타우마틴, 스테비아 추출물과 같은 천연 감미제; 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 건강음료 조성물 100 ml 당 일반적으로 약 0.01 ~ 0.04 g, 구체적으로 약 0.02 ~ 0.03 g이 될 수 있다.As an example of the food composition of the present invention, it may be used as a health drink composition, and in this case, it may contain various flavoring agents or natural carbohydrates, etc. as an additional ingredient, such as a conventional beverage. The natural carbohydrates described above include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Polysaccharides such as dextrin and cyclodextrin; It may be a sugar alcohol such as xylitol, sorbitol, and erythritol. Sweeteners include natural sweeteners such as taumatin and stevia extract; Synthetic sweeteners such as saccharin and aspartame can be used. The ratio of the natural carbohydrate may be generally about 0.01 ~ 0.04 g, specifically about 0.02 ~ 0.03 g per 100 ml of the health beverage composition of the present invention.
상기 외에 건강음료 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산, 펙트산의 염, 알긴산, 알긴산의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올 또는 탄산화제 등을 함유할 수 있다. 그 밖에 천연 과일주스, 과일주스 음료, 또는 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 혼합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 건강음료 조성물 100 중량부당 0.01 ~ 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, health beverage compositions include various nutrients, vitamins, electrolytes, flavoring agents, colorants, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, It may contain alcohol or a carbonation agent. In addition, it may contain flesh for the manufacture of natural fruit juice, fruit juice beverage, or vegetable beverage. These ingredients may be used independently or in combination. Although the ratio of these additives is not very important, it is generally selected from 0.01 to 0.1 parts by weight per 100 parts by weight of the health beverage composition of the present invention.
본 발명의 또 다른 실시양태는 옥수수수염 추출물 또는 이의 분획물을 포함하는 아토피 피부염의 예방 또는 개선용 의약외품 조성물을 제공한다.Another embodiment of the present invention provides a quasi-drug composition for preventing or improving atopic dermatitis comprising a corn beard extract or a fraction thereof.
이때, 상기 옥수수수염, 추출물, 분획물, 아토피 피부염, 예방 및 개선의 정의는 상기에서 설명한 바와 같다.At this time, the definition of corn beard, extract, fraction, atopic dermatitis, prevention and improvement are as described above.
본 발명의 용어, "의약외품"은 사람이나 동물의 질병을 치료, 경감, 처치 또는 예방할 목적으로 사용되는 섬유, 고무제품 또는 이와 유사한 것, 인체에 대한 작용이 약하거나 인체에 직접 작용하지 않으며, 기구 또는 기계가 아닌 것과 이와 유사한 것, 감염 예방을 위하여 살균, 살충 및 이와 유사한 용도로 사용되는 제제 중 하나에 해당하는 물품으로서, 사람이나 동물의 질병을 진단, 치료, 경감, 처치 또는 예방할 목적으로 사용하는 물품 중 기구, 기계 또는 장치가 아닌 것 및 사람이나 동물의 구조와 기능에 약리학적 영향을 줄 목적으로 사용하는 물품 중 기구, 기계 또는 장치가 아닌 것을 제외한 물품을 의미하며, 피부 외용제 및 개인위생용품도 포함한다.The term "quasi-drug" of the present invention refers to fibers, rubber products, or the like, which are used for the purpose of treating, alleviating, treating or preventing diseases of humans or animals, weakly acting on the human body or not directly acting on the human body, and Or non-machine or similar, as an item that is one of the preparations used for sterilization, insecticide and similar purposes to prevent infection, and used for the purpose of diagnosing, treating, alleviating, treating or preventing diseases of humans or animals. It refers to items that are not instruments, machines, or devices among the items that are used, and items that are not instruments, machines, or devices among items used for the purpose of pharmacologically affecting the structure and function of humans or animals, and are intended for skin external use and personal hygiene. Includes supplies.
본 발명의 옥수수수염 추출물은 아토피의 예방 또는 개선을 목적으로 의약외품 조성물에 첨가할 경우, 상기 추출물을 그대로 첨가하거나 다른 의약외품 성분과 함께 사용할 수 있고, 통상적인 방법에 따라 적절하게 사용할 수 있다. 유효 성분의 혼합양은 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다.When the corn beard extract of the present invention is added to a quasi-drug composition for the purpose of preventing or improving atopy, the extract may be added as it is or used with other quasi-drug ingredients, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment).
상기 의약외품 조성물은 특별히 이에 제한되지 않으나, 개인위생용품, 피부외용제, 소독청결제, 샤워폼, 물티슈, 세제비누, 핸드워시, 마스크 또는 연고제를 포함한다. 상기 피부외용제는 특별히 이에 제한되지 않으나, 구체적으로 연고제, 로션제, 스프레이제, 패취제, 크림제, 산제, 현탁제, 겔제 또는 젤의 형태로 제조되어 사용될 수 있다. 상기 개인위생용품에는 특별히 이에 제한되지 않으나, 구체적으로 비누, 물티슈, 휴지, 샴푸, 치약, 모발 손질 제품, 에어프레쉬너 겔 또는 세정 겔일 수 있다. The quasi-drug composition is not particularly limited thereto, but includes personal hygiene products, external skin preparations, disinfectant cleansers, shower foams, wet tissues, detergent soaps, hand wash, masks or ointments. The external preparation for skin is not particularly limited thereto, but may be specifically prepared and used in the form of an ointment, lotion, spray, patch, cream, powder, suspension, gel or gel. The personal hygiene product is not particularly limited thereto, but may be specifically soap, wet tissue, tissue paper, shampoo, toothpaste, hair care product, air freshener gel, or washing gel.
본 발명의 또 다른 실시양태는 옥수수수염 추출물 또는 이의 분획물을 포함하는 아토피 피부염의 예방 또는 개선용 화장료 조성물을 제공한다.Another embodiment of the present invention provides a cosmetic composition for preventing or improving atopic dermatitis comprising a corn beard extract or a fraction thereof.
이때, 상기 옥수수수염, 추출물, 분획물, 아토피 피부염, 예방 및 개선의 정의는 상기에서 설명한 바와 같다.At this time, the definition of corn beard, extract, fraction, atopic dermatitis, prevention and improvement are as described above.
상기 옥수수수염 추출물은 상기 조성물에 대하여 약학 조성물과 마찬가지로 상기 추출물을 조성물 총 중량에 대하여 0.1 중량% 내지 20 중량%의 비율로 포함할 수 있다. 구체적으로 조성물 총 중량에 대하여 0.1 중량% 내지 5 중량%, 더욱 구체적으로 0.4 내지 0.6 중량%, 더더욱 구체적으로 0.5 중량%의 비율로 포함되나, 이에 제한되지 않는다. The corn beard extract may contain the extract in an amount of 0.1% to 20% by weight based on the total weight of the composition, as in the pharmaceutical composition. Specifically, it is included in a ratio of 0.1% to 5% by weight, more specifically 0.4 to 0.6% by weight, and even more specifically 0.5% by weight based on the total weight of the composition, but is not limited thereto.
본 발명의 화장료 조성물에 포함되는 성분으로는 상기 추출물 이외에 화장료 조성물에 통상적으로 이용되는 성분들을 포함하며, 예를 들어 물, 계면활성제, 보습제, 저급알코올, 킬레이트제, 살균제, 산화방지제, 방부제, 색소 및 향료로 이루어지는 군으로부터 선택되는 하나 이상의 첨가제를 추가로 포함할 수 있다.Ingredients included in the cosmetic composition of the present invention include ingredients commonly used in cosmetic compositions in addition to the above extracts, for example, water, surfactants, moisturizers, lower alcohols, chelating agents, fungicides, antioxidants, preservatives, pigments And it may further include one or more additives selected from the group consisting of fragrances.
또한, 상기 화장료 조성물은 통상적으로 제조되는 어떠한 제형으로도 제조될수 있으며, 예를 들어 용액, 유탁액, 현탁액, 페이스트, 크림, 로션, 겔, 파우더, 스프레이, 계면활성제-함유 클린징, 오일, 비누, 액체 세정료, 입욕제, 파운데이션, 메이크업베이스, 에센스, 화장수, 폼, 팩, 유연수, 선스크린 크림 또는 선오일 등으로 제형화 될 수 있으나, 이에 제한되지 않는다. In addition, the cosmetic composition may be prepared in any conventionally prepared formulation, for example, solution, emulsion, suspension, paste, cream, lotion, gel, powder, spray, surfactant-containing cleansing, oil, soap, It may be formulated as a liquid detergent, bath agent, foundation, makeup base, essence, lotion, foam, pack, softening water, sunscreen cream or sun oil, but is not limited thereto.
본 발명의 제형이 용액 또는 유탁액인 경우에는 담체 성분으로서 용매, 용해화제 또는 유탁화제가 이용되고, 예컨대 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 있다.When the formulation of the present invention is a solution or emulsion, a solvent, a solubilizing agent or an emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan.
본 발명의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상의 희석제, 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 또는 트라칸트 등이 이용될 수 있다.When the formulation of the present invention is a suspension, liquid diluents such as water, ethanol or propylene glycol as carrier components, ethoxylated isostearyl alcohol, suspending agents such as polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, crystallites Sex cellulose, aluminum metahydroxide, bentonite, or tracant may be used.
본 발명의 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물성유, 식물성유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될 수 있다.When the formulation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, or zinc oxide may be used as carrier components. I can.
본 발명의 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다.When the formulation 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. In particular, in the case of a spray, additionally chlorofluorohydrocarbon, propane / May contain propellants such as butane or dimethyl ether.
본 발명의 제형이 계면-활성제 함유 클린징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르 설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성유, 라놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.When the formulation of the present invention is a surfactant containing cleansing, as a carrier component, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, or ethoxylated glycerol fatty acid esters may be used.
또한, 상기 화장료 조성물에 포함되는 성분들은 피부 과학 분야에서 일반적으로 사용되는 양으로 포함될 수 있다.In addition, the ingredients included in the cosmetic composition may be included in an amount generally used in the field of dermatology.
본 발명의 옥수수수염 추출물은 항염증 효과를 나타낼 뿐만 아니라, 아토피 피부염의 발병원인 중의 하나를 억제하는 효과를 나타냄을 확인하였으므로, 본 발명의 옥수수수염 추출물은 아토피 피부염의 예방 또는 치료에 널리 활용될 수 있을 것이다.Since it was confirmed that the corn beard extract of the present invention not only exhibits anti-inflammatory effects, but also suppresses one of the causes of atopic dermatitis, the corn beard extract of the present invention can be widely used in the prevention or treatment of atopic dermatitis. There will be.
도 1은 LPS 처리된 대식세포(Raw 264.7)에서 NO 생성량에 미치는 옥수수수염 추출물의 효과를 비교한 결과를 나타내는 그래프이다.
도 2는 LPS 처리된 대식세포(Raw 264.7)에서 TNF-α 생성량에 미치는 옥수수수염 추출물의 효과를 비교한 결과를 나타내는 그래프이다.
도 3은 INF-r 와 TNF-α로 처리된 상피세포(HaCaT 세포)에서 TARC 생성량에 미치는 옥수수수염 추출물의 효과를 비교한 결과를 나타내는 그래프이다.1 is a graph showing the result of comparing the effect of corn beard extract on the amount of NO production in LPS-treated macrophages (Raw 264.7).
Figure 2 is a graph showing the results of comparing the effect of corn beard extract on the amount of TNF-α production in LPS-treated macrophages (Raw 264.7).
3 is a graph showing the result of comparing the effect of corn beard extract on TARC production in epithelial cells (HaCaT cells) treated with INF-r and TNF-α.
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 through examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.
실시예Example 1: 옥수수수염 추출물( 1: Corn beard extract ( NICSNICS -1, -One, NICSNICS -3) 제조-3) Manufacturing
옥수수수염 시료는 농촌진흥청 국립식량과학원에서 재배 생산된 '광평옥'의 옥수수수염을 채취하여 사용하였다.Corn beard samples were used by collecting corn beard from'Gwangpyeongok' cultivated by the National Institute of Food Science, Rural Development Administration.
상기 시료를 채취한 즉시 약 5-10 cm의 크기로 세절하고, 세절된 옥수수수염 1 kg에 95% 주정(프레타놀 A, Reagents Duksan, Gyeonggi-do, Korea) 2000 ㎖를 투입하여 직사광선이 비추지 않는 곳에서 25℃의 온도로 9일간 추출하였다. 이로부터 수득한 추출물을 탈지면으로 1차여과 후 No. 3 거름종이로 2차 여과하고 감압 농축하여 옥수수수염 조추출물을 얻었다. 얻어진 옥수수수염 조추출물은 C18(Preparative C18 reverse phase bulk packing material, 125, 55-105 μm, Waters, Milford, MA) 분말로 충진된 컬럼에 주입하여 초순수 중량%의 초기조성에서 에탄올(ethanol) 중량%만으로 된 기울기법으로 이동상을 흘려주어 옥수수수염 추출물(NICS-1)을 수득하였다. 상기의 과정을 거쳐 얻어진 옥수수수염 추출물(NICS-1)은 순도가 높은 메이신을 얻기 위해 C18 컬럼에 재주입시켜 메이신을 다량 함유하고 있는 분취물(fraction)을 취하고 이를 다시 감압농축시킨 후 순도가 높은 메이신 고형물을 포함하는 옥수수수염 추출물(NICS-3)을 수득하였다.Immediately after collecting the sample, cut it into pieces of about 5-10 cm, and add 2000 ml of 95% alcohol (Pretanol A, Reagents Duksan, Gyeonggi-do, Korea) to 1 kg of chopped corn beard to avoid direct sunlight. Extracted for 9 days at a temperature of 25 ℃ in the place not. The extract obtained therefrom was first filtered with cotton wool and then No. 3 Secondary filtration with filter paper and concentrated under reduced pressure to obtain a crude corn extract. The obtained crude cornstarch extract was injected into a column filled with C18 (Preparative C18 reverse phase bulk packing material, 125, 55-105 μm, Waters, Milford, MA) powder, and ethanol (ethanol) wt% in the initial composition of ultrapure water wt% The mobile phase was flowed by using the gradient method with only a bay to obtain a corn beard extract (NICS-1). Corn beard extract (NICS-1) obtained through the above process was re-injected into a C18 column to obtain high purity macin to take a fraction containing a large amount of macin and concentrated under reduced pressure. Corn beard extract (NICS-3) containing a solid mayin was obtained.
실시예Example 2: 세포배양 및 세포 생존율 측정 2: Cell culture and cell viability measurement
RAW 264.7 세포(mouse macrophage cell, ATCC) 및 HaCaT 세포(human keratinocyte, HaCaT, ATCC) 은 37℃, 5% CO2 조건에서 10% FBS, 페니실린(100 U/㎖) 및 스트렙토마이신(100 ㎍/㎖)이 첨가된 DMEM 배지로 배양되었다. 배양 3일 간격으로 충분히 증식되면, 1 ㎖의 0.25% 트립신-EDTA 용액을 넣고 실온에서 1분간 처리한 다음 세포를 탈착하여 계대배양하였다. 탈착된 세포는 10% FBS가 첨가된 DMEM 배양액 10 ㎖에 부유시킨 다음, 새로운 배양용기에 옮겨 1:2의 비율(split ratio)로 CO2 배양기(37℃, 5% CO2)에서 배양하였다. RAW 264.7 cells (mouse macrophage cells, ATCC) and HaCaT cells (human keratinocyte, HaCaT, ATCC) were 10% FBS, penicillin (100 U/ml) and streptomycin (100 μg/ml) at 37°C and 5% CO2 It was cultured with the added DMEM medium. When sufficiently proliferated every 3 days of culture, 1 ml of 0.25% trypsin-EDTA solution was added and treated at room temperature for 1 minute, and then the cells were detached and subcultured. The detached cells were suspended in 10 ml of DMEM culture medium to which 10% FBS was added, and then transferred to a new culture vessel and cultured in a CO 2 incubator (37° C., 5% CO 2 ) at a ratio of 1:2.
상기 제조된 두 가지 옥수수수염 추출물(NICS-1, NICS-3)이 세포독성을 보이는지 확인하기 위해 세포 생존율을 측정하였다. 세포 생존율은 WST-1 반응액(cell proliferation reagent WST-1, Roche, Bern, Swiss)을 DMEM 배지에 1/10로 희석하고 이를 각 웰당 100 ㎕씩 처리하여 1시간 동안 반응시킨 후, 450 nm에서 흡광도를 측정하였다. 그 결과, 두 가지 추출물(NICS-1, NICS-3) 모두 세포독성을 나타내지 않음을 확인하였다.Cell viability was measured to confirm whether the two prepared corn beard extracts (NICS-1, NICS-3) showed cytotoxicity. The cell viability was determined by diluting the WST-1 reaction solution (cell proliferation reagent WST-1, Roche, Bern, Swiss) to 1/10 in DMEM medium and treating it with 100 µl per well and reacting for 1 hour at 450 nm. The absorbance was measured. As a result, it was confirmed that neither of the two extracts (NICS-1, NICS-3) showed cytotoxicity.
실시예Example 3: NO 생성 억제 평가 통한 항염증 효과 3: Anti-inflammatory effect through NO production inhibition evaluation
NO는 염증반응, 종양형성, 고혈압, 당뇨 및 피부염 등과 같은 여러 가지 질병에서 중요한 역할을 하는 것으로 알려져 있다. 일반적으로 큰포식세포에서 LPS의 자극을 받으면 염증 매개 인자인 NO를 대량으로 생산함으로써 염증반응을 유도한다고 알려져 있다. NICS-1 및 NICS-3를 RAW 264.7 세포에 처리 할 경우 NO 생성에 미치는 영향을 알아보기 위하여 각각 샘플농도 10, 50 및 100 ㎍/㎖를 처리하고 30분 후에 LPS (1 ㎍/㎖)로 자극하여 24시간 배양 후 NO생성량을 확인하였다. NO is known to play an important role in various diseases such as inflammatory response, tumor formation, hypertension, diabetes and dermatitis. In general, it is known to induce an inflammatory response by producing large amounts of NO, an inflammatory mediator, when stimulated by LPS in macrophages. In order to investigate the effect of processing NICS-1 and NICS-3 on RAW 264.7 cells on NO production, sample concentrations of 10, 50 and 100 ㎍/mL were treated, respectively, and stimulated with LPS (1 ㎍/mL) after 30 minutes. Then, after 24 hours incubation, the amount of NO production was confirmed.
구체적으로, 96웰 플레이트에 웰당 5×104 세포수의 Raw 264.7 세포를 분주한 후 18시간 동안 배양하였다. 배양 후 시료를 농도에 따라 처리하고 30분 후 염증 반응 유도 인자인 LPS(lipopolysaccharide)를 처리하여 24시간 동안 배양하였다. 생성된 NO의 양은 그리스 시약(Griess reagent)을 이용하여 세포 배양액 중에 존재하는 NO2 -의 형태로 측정하였다. 세포 배양 상등액 100 ㎕와 그리스시약 100 ㎕를 혼합하여 10분 동안 상온에서 반응 시킨 후, 540 nm에서 흡광도를 측정하였다. 이때, 배양액의 NO농도는 아질산소듐(sodium nitrite)의 표준물질(standard)로 비교하였다(도 1).Specifically, Raw 264.7 cells of 5×10 4 cells per well were dispensed into a 96-well plate and cultured for 18 hours. After incubation, the sample was treated according to the concentration, and after 30 minutes, LPS (lipopolysaccharide), which is an inflammatory response inducing factor, was treated and incubated for 24 hours. The amount of NO produced was measured in the form of NO 2 − present in the cell culture solution using a Grease reagent. 100 µl of the cell culture supernatant and 100 µl of grease reagent were mixed and reacted at room temperature for 10 minutes, and the absorbance was measured at 540 nm. At this time, the NO concentration of the culture medium was compared with the standard of sodium nitrite (Fig. 1).
도 1은 LPS 처리된 대식세포(Raw 264.7)에서 NO 생성량에 미치는 옥수수수염 추출물의 효과를 비교한 결과를 나타내는 그래프이다.1 is a graph showing the result of comparing the effect of corn beard extract on the amount of NO production in LPS-treated macrophages (Raw 264.7).
도 1에서 보듯이, LPS 단독 처리구에서 NO생성량이 무처리 군에 비해서 크게 증가하였으나, 옥수수염 추출물(NICS-1 및 NICS-3)을 처리한 군에서는 농도 의존적으로 NO생성량이 감소함을 확인하였다. As shown in FIG. 1, it was confirmed that the amount of NO production in the LPS-only treatment group increased significantly compared to the untreated group, but in the group treated with corn salt extract (NICS-1 and NICS-3), the amount of NO production decreased in a concentration-dependent manner. .
구체적으로, LPS 단독 처리 시 NO생성량이 49.43 nM로 나타났으나 추출물 중 정제가 1번 된 NICS-1를 100 ㎍/㎖ 농도로 병행 처리 하였을 때 21.43 nM로 약 50% 이상 감소하는 것으로 나타났다. 또한, 옥수수수염 추출물 중 정제가 2번 이루어진 NICS-3는 각각 50 ㎍/㎖ 및 100 ㎍/㎖ 처리 시 각각 26.25 nM 및 3.60 nM 농도로 NO생성량이 크게 감소하는 것으로 나타났다. 즉, LPS에 의한 NO 생성 억제 효능은 NICS-1 보다 NICS-3를 처리하였을 때 더 우수한 억제 효능이 있음을 알 수 있었다.Specifically, when treated with LPS alone, the amount of NO produced was 49.43 nM, but when the NICS-1, which was purified once among the extracts, was treated in parallel at a concentration of 100 μg/ml, it was found to decrease by more than 50% to 21.43 nM. In addition, it was found that the amount of NO production in NICS-3, which was purified twice among corn beard extracts, was significantly reduced at 26.25 nM and 3.60 nM concentrations when treated with 50 µg/ml and 100 µg/ml, respectively. In other words, it was found that the inhibitory effect of NO generation by LPS was better when NICS-3 was treated than NICS-1.
실시예Example 4: 4: TNFTNF -α 생성 억제 평가 통한 항염증 효과Anti-inflammatory effect through evaluation of -α production inhibition
TNF-α는 LPS 반응의 주요 매개체로 염증의 개시 및 유지에 핵심적 작용을 하여 염증성 병변 과정에서 증가된 발현을 보이며, 특히 만성 염증 질환과 밀접한 관련이 있다. 이러한 TNF-α는 내분비와 외분비를 통해 자신과 다른 대식세포의 TNF-α 수용체에 리간드로 결합해 다양한 염증 매개 전사 인자들을 활성화시켜 TNF-α을 발현시키는 메커니즘을 통해 염증을 심화시킨다. 따라서, 옥수수수염 추출물이 RAW 264.7 세포에서 TNF-α 분비 영향에 대해 분석하였다.TNF-α is a major mediator of the LPS response and plays a key role in the initiation and maintenance of inflammation, showing increased expression in the process of inflammatory lesions, and is particularly closely related to chronic inflammatory diseases. Such TNF-α, through endocrine and exocrine secretion, binds to TNF-α receptors of itself and other macrophages as a ligand, activates various inflammatory-mediated transcription factors, and intensifies inflammation through a mechanism that expresses TNF-α. Therefore, the corn beard extract was analyzed for the effect of TNF-α secretion in RAW 264.7 cells.
구체적으로, 48웰 플레이트에 웰당 1×106 세포수의 Raw 264.7 세포를 분주한 후 24시간 동안 배양하였다. 배양 후 세포를 12시간동안 기아상태를 유지시킨 다음 LPS 1 ㎍/㎖와 각각의 옥수수수염 추출물(0, 10, 50, 100 ㎍/㎖)을 단독 또는 혼합으로 처리하여 24시간 동안 배양 하였다. 배양된 세포의 배지를 수거하여 ELISA법으로 TNF-α 양을 측정하였다. 또한, 바닥에 부착되어 있는 세포는 PBS로 세척한 후, 1N 수산화나트륨(NaOH)로 세포용해(lysis) 시켜 총 단백질 양을 측정하여 일정 단백질에 대한 TNF-α 생성양을 측정하였다. 이때, 각각의 TNF-α 양과 단백질 양은 보정선에 따라 측정하였다(도 2).Specifically, Raw 264.7 cells of 1×10 6 cells per well were dispensed into a 48-well plate and cultured for 24 hours. After culture, the cells were starved for 12 hours, and then
도 2는 LPS 처리된 대식세포(Raw 264.7)에서 TNF-α 생성량에 미치는 옥수수수염 추출물의 효과를 비교한 결과를 나타내는 그래프이다.Figure 2 is a graph showing the results of comparing the effect of corn beard extract on the amount of TNF-α production in LPS-treated macrophages (Raw 264.7).
도 2에서 보듯이, LPS 단독 처리구에서는 3401.09 pg/㎖ 의 높은 TNF-α 생성량을 나타냈으나, 옥수수수염 추출물(NICS-1 및 NICS-3)을 각각 함께 처리한 결과 100 ㎍/㎖에서 1862.76 및 1364.25 pg/㎖으로 억제되었다. 특히, NICS-3의 경우 10 ㎍/㎖ 처리구에서는 2621.80 pg/㎖ 이며 50 ㎍/㎖ 처리구에서는 2195.97 pg/㎖으로 농도 의존적으로 생성량이 감소하는 효과를 확인하였다. As shown in FIG. 2, the LPS alone treatment group showed a high TNF-α production amount of 3401.09 pg/ml, but as a result of treatment with corn beard extracts (NICS-1 and NICS-3), respectively, 1862.76 and at 100 µg/ml It was inhibited at 1364.25 pg/ml. In particular, in the case of NICS-3, it was confirmed that the concentration-dependently decreased production amount was 2621.80 pg/ml in the 10 µg/ml treatment group and 2195.97 pg/ml in the 50 µg/ml treatment group.
상기 결과로부터, 옥수수수염 추출물(NICS-1 및 NICS-3)이 RAW 264.7 세포에서 TNF-α 분비를 억제하여 항염증 기능에 관여함을 알 수 있었다.From the above results, it was found that corn beard extracts (NICS-1 and NICS-3) inhibit TNF-α secretion in RAW 264.7 cells and are involved in anti-inflammatory function.
실시예Example 5: 아토피 피부염 개선 효과 5: Atopic dermatitis improvement effect
옥수수수염 추출물이 상피세포(HaCaT 세포)에서 생산되는 염증성 사이토카인(Th2 케모카인)의 일종인 TARC(thymus and activation regualted chemokine)의 생산에 미치는 영향을 분석하였다.The effect of corn beard extract on the production of thymus and activation regualted chemokine (TAC), a kind of inflammatory cytokine (Th2 chemokine) produced in epithelial cells (HaCaT cells), was analyzed.
구체적으로, 상피세포인 HaCaT 세포를 48웰 플레이트에 웰당 1×106 세포수로 분주하고 24시간동안 배양하였다. 배지를 제거하고 10 ng/㎖ 의 INF-r 와 10 ng/㎖의 TNF-α 및 각각의 옥수수수염 추출물을 각각의 농도로 배지에 희석한 후 처리하였다. 24시간 배양후 배양액을 취하여 Human TARC 면역분석키트(Immunoassay kit, R&D systems, PDDN00)을 사용하여 TARC 분비량을 측정한 후 측정된 TARC 양은 총 단백질 양으로 보정하였다(도 3).Specifically, HaCaT cells, which are epithelial cells, were dispensed into a 48-well plate at 1×10 6 cells per well and cultured for 24 hours. The medium was removed, 10 ng/mL of INF-r, 10 ng/mL of TNF-α, and each corn beard extract were diluted in the medium at respective concentrations, followed by treatment. After 24 hours of incubation, the culture medium was taken and the amount of TARC secretion was measured using a Human TARC immunoassay kit (Immunoassay kit, R&D systems, PDDN00), and the measured TARC amount was corrected to the total protein amount (FIG. 3).
도 3은 INF-r 와 TNF-α로 처리된 상피세포(HaCaT 세포)에서 TARC 생성량에 미치는 옥수수수염 추출물의 효과를 비교한 결과를 나타내는 그래프이다.3 is a graph showing the result of comparing the effect of corn beard extract on TARC production in epithelial cells (HaCaT cells) treated with INF-r and TNF-α.
도 3에서 보듯이, 아무런 처리도 하지 않은 대조군에 비하여, IFN-γ 및 TNF-α를 처리한 실험군에서 유의성 있는 TARC 생성의 증가를 보여 IFN-γ 및 TNF-α의 처리가 HaCaT 세포의 아토피를 효과적으로 유도하였음을 알 수 있었다. As shown in FIG. 3, compared to the control group without any treatment, the experimental group treated with IFN-γ and TNF-α showed a significant increase in TARC production, so that treatment with IFN-γ and TNF-α increased atopy of HaCaT cells. It can be seen that it was effectively induced.
또한, NICS-1의 경우 IFN-γ 및 TNF-α를 처리하지 않은 대조군에 대비하여 각각 925.3%, 580.9% 및 161.8%의 TARC가 생성되며, 이는 농도 의존적으로 감소하였고, NICS-3의 경우 대조군에 대비하여 각각 301.5%, 1210.8% 및 924.9%의 TARC가 생성되었으며, NICS-1과 비슷하게 농도 의존적으로 감소함을 확인하였다. 즉, 본 발명의 옥수수수염 추출물(NICS-1 및 NICS-3)은 상피세포인 HaCaT 세포에서 TARC 생성을 억제하는 효과를 나타냄을 알 수 있었다.In addition, in the case of NICS-1, 925.3%, 580.9%, and 161.8% of TARC were produced, respectively, compared to the control group not treated with IFN-γ and TNF-α, which decreased in a concentration-dependent manner, and in the case of NICS-3, the control group In contrast, 301.5%, 1210.8% and 924.9% of TARC were generated, respectively, and it was confirmed that the concentration-dependent decrease was similar to that of NICS-1. That is, it was found that the corn beard extract (NICS-1 and NICS-3) of the present invention exhibits an effect of inhibiting TARC production in HaCaT cells, which are epithelial cells.
상기 결과로부터, 본 발명의 옥수수수염 추출물은 상피세포에서 생산되는 염증성 사이토카인의 생성을 억제하여, 아토피 피부염을 치료하는 효과를 나타낼 수 있음을 알 수 있었다.From the above results, it was found that the corn beard extract of the present invention can exhibit an effect of treating atopic dermatitis by inhibiting the production of inflammatory cytokines produced in epithelial cells.
이상의 설명으로부터, 본 발명이 속하는 기술분야의 당업자는 본 발명이 그 기술적 사상이나 필수적 특징을 변경하지 않고서 다른 구체적인 형태로 실시될 수 있다는 것을 이해할 수 있을 것이다. 이와 관련하여, 이상에서 기술한 실시 예들은 모든 면에서 예시적인 것이며 한정적인 것이 아닌 것으로서 이해해야만 한다. 본 발명의 범위는 상기 상세한 설명보다는 후술하는 특허 청구범위의 의미 및 범위 그리고 그 등가 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.From the above description, those skilled in the art to which the present invention pertains will be able to understand that the present invention can be implemented in other specific forms without changing the technical spirit or essential features thereof. In this regard, the embodiments described above are illustrative in all respects and should be understood as non-limiting. The scope of the present invention should be construed that all changes or modifications derived from the meaning and scope of the claims to be described later rather than the above detailed description, and equivalent concepts thereof, are included in the scope of the present invention.
Claims (13)
A pharmaceutical composition for the prevention or treatment of atopic dermatitis, comprising a corn beard extract or a fraction thereof.
상기 옥수수수염 추출물은 LPS(lipopolysaccharide)로 자극된 대식세포에서 생성되는 NO(nitric oxide) 및 TNF-α(tumor necrosis factor-α)의 수준을 감소시키는 것인, 아토피 피부염의 예방 또는 치료용 약학 조성물.
The method of claim 1,
The corn beard extract is to reduce the level of NO (nitric oxide) and TNF-α (tumor necrosis factor-α) produced in macrophages stimulated with LPS (lipopolysaccharide), a pharmaceutical composition for the prevention or treatment of atopic dermatitis .
상기 대식세포는 RAW 264.7 세포인 것인, 아토피 피부염의 예방 또는 치료용 약학 조성물.
The method of claim 2,
The macrophages are RAW 264.7 cells, a pharmaceutical composition for the prevention or treatment of atopic dermatitis.
상기 옥수수수염 추출물은 IFN-γ(Interferon-γ) 및 TNF-α(tumor necrosis factor-α)로 자극된 상피세포에서 생성되는 염증성 사이토카인의 수준을 감소시키는 것인, 아토피 피부염의 예방 또는 치료용 약학 조성물.
The method of claim 1,
The corn beard extract is to reduce the level of inflammatory cytokines produced in epithelial cells stimulated with IFN-γ (Interferon-γ) and TNF-α (tumor necrosis factor-α), for the prevention or treatment of atopic dermatitis Pharmaceutical composition.
상기 상피세포는 HaCaT 세포인 것인, 아토피 피부염의 예방 또는 치료용 약학 조성물.
The method of claim 4,
Wherein the epithelial cells are HaCaT cells, a pharmaceutical composition for the prevention or treatment of atopic dermatitis.
상기 염증성 사이토카인은 TARC(thymus and activation regualted chemokine)인 것인, 아토피 피부염의 예방 또는 치료용 약학 조성물.
The method of claim 4,
The inflammatory cytokine is TARC (thymus and activation regualted chemokine) that is, a pharmaceutical composition for the prevention or treatment of atopic dermatitis.
상기 추출물은 옥수수수염을 물, 탄소수 1 내지 4의 알코올 및 이들의 혼합 용매로 이루어진 군에서 선택된 1종 이상의 용매로 추출하여 수득한 것인, 아토피 피부염의 예방 또는 치료용 약학 조성물.
The method of claim 1,
The extract is obtained by extracting corn beard with one or more solvents selected from the group consisting of water, alcohols having 1 to 4 carbon atoms, and mixed solvents thereof.
상기 분획물은 옥수수수염 추출물을 물, 탄소수 1 내지 4의 알코올, 헥산(Hexane), 에틸 아세테이트(Ethyl acetate), 클로로포름(Chloroform), 디클로로메탄(Dichloromethane) 및 이들의 혼합용매로 구성되는 군으로부터 선택되는 용매로 분획하여 수득한 것인, 아토피 피부염의 예방 또는 치료용 약학 조성물.
The method of claim 1,
The fraction is selected from the group consisting of water, alcohol having 1 to 4 carbon atoms, hexane (Hexane), ethyl acetate (Ethyl acetate), chloroform (Chloroform), dichloromethane (Dichloromethane) and a mixed solvent thereof. A pharmaceutical composition for the prevention or treatment of atopic dermatitis, which is obtained by fractionation with a solvent.
상기 조성물은 약학적으로 허용되는 담체, 부형제 또는 희석제를 추가로 포함하는 것인, 아토피 피부염의 예방 또는 치료용 약학 조성물.
The method of claim 1,
The composition further comprises a pharmaceutically acceptable carrier, excipient or diluent, a pharmaceutical composition for the prevention or treatment of atopic dermatitis.
A method of treating atopic dermatitis, comprising administering the pharmaceutical composition of any one of claims 1 to 9 to an individual suspected of having atopic dermatitis, excluding humans.
A food composition for improving atopic dermatitis comprising a corn beard extract or a fraction thereof.
A quasi-drug composition for the prevention or improvement of atopic dermatitis comprising a corn beard extract or a fraction thereof.
A cosmetic composition for the prevention or improvement of atopic dermatitis comprising a corn beard extract or a fraction thereof.
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WO2022055331A1 (en) | 2020-09-14 | 2022-03-17 | 주식회사 엘지에너지솔루션 | Method for manufacturing gel polymer electrolyte secondary battery and gel polymer electrolyte secondary battery manufactured thereby |
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WO2022055331A1 (en) | 2020-09-14 | 2022-03-17 | 주식회사 엘지에너지솔루션 | Method for manufacturing gel polymer electrolyte secondary battery and gel polymer electrolyte secondary battery manufactured thereby |
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