KR20190003415A - Composition for preventing or treating of Th2-mediated immune disease or inflammatory disease comprising enzyme-treated ellagic acid as an active ingredient - Google Patents
Composition for preventing or treating of Th2-mediated immune disease or inflammatory disease comprising enzyme-treated ellagic acid as an active ingredient Download PDFInfo
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- KR20190003415A KR20190003415A KR1020180076036A KR20180076036A KR20190003415A KR 20190003415 A KR20190003415 A KR 20190003415A KR 1020180076036 A KR1020180076036 A KR 1020180076036A KR 20180076036 A KR20180076036 A KR 20180076036A KR 20190003415 A KR20190003415 A KR 20190003415A
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- Prior art keywords
- disease
- enzyme
- treated
- composition
- ellagic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
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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
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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
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
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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
- A23V2200/304—Foods, ingredients or supplements having a functional effect on health having a modulation effect on allergy and risk of allergy
Abstract
Description
본 발명은 효소가 처리된 엘라그산을 유효성분으로 포함하는, Th2-매개 면역질환 또는 염증성 질환의 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for the prophylaxis or treatment of a Th2-mediated immune disease or inflammatory disease, which comprises an enzyme-treated elastase as an active ingredient.
Thl(type 1 helper T)과 Th2(type 2 helper T) 세포가 생산하는 사이토카인에 의해 조절되는 면역균형을 Thl/Th2 균형이라고 하며, Thl 세포는 세포성 면역의 조절에 중요하고, Th2 세포는 체액성 조절에 중요한 역할을 한다. 정상상태에서는 Thl의 분화에 중요한 IFN-γ를 중심으로 한 사이토카인과 Th2의 분화에 중요한 IL-4를 중심으로 한 사이토카인이 서로 간섭하면서 Thl/Th2 균형을 일정하게 유지하고 있으나, Thl/Th2 균형이 깨지면 다양한 면역질환이 유발될 수 있다. 예컨대, Thl에 편향한 경우에는 세포성 면역이 부활하여 감염저항성이 증강하고, Th2에 편향한 경우에는 감염저항성이 감소하고, 역으로 알레르기가 증강한다고 알려져 있다. The immune balance regulated by cytokines produced by Th1 (
염증반응은 생체 혹은 조직에 기질적 변화를 가져오는 화학적 물질, 세균 감염 및 물리적 작용에 의해 발생된 손상 부위를 재생하려는 복구기전이다. 유해한 자극, 감염 및 외상 등에 의해 염증이 발현되면 국소적으로 염증성 성분과 같은 혈관 활성 물질이 유리되어 염증을 유발하는데, 이와 같은 염증반응이 지속되면 오히려 점막손상을 촉진함에 따라 발적, 발열, 종창, 동통, 기능장애 등으로 인한 류마티스 관절염, 동맥경화증, 위염, 천식 등의 염증성질환을 유발할 수 있다.Inflammation is a mechanism of recovery to regenerate damaged areas caused by chemical substances, bacterial infections, and physical effects that cause changes in organisms or tissues. When inflammation is manifested by harmful stimuli, infections and trauma, inflammation is induced by local release of vasoactive substances such as inflammatory components. If the inflammatory reaction is continued, mucous membrane damage is promoted, resulting in redness, fever, swelling, Inflammatory diseases such as rheumatoid arthritis, arteriosclerosis, gastritis, and asthma caused by pain, dysfunction, and the like.
대식세포는 선천면역뿐만 아니라 획득면역 등 다양한 숙주반응에 대하여 항상성 유지에 관여하며, 염증 반응 시에는 nitric oxide(NO) 및 다양한 cytokine을 생산하여 감염 초기에 생체방어에 중요한 역할을 하는 세포이다. RAW 264.7과 같은 대식세포 또는 단핵구는 그람 음성균의 세포외막에 존재하는 내독소인 lipopolysaccharide(LPS)의 자극에 의해 tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) 및 IL-6와 같은 염증매개성 cytokine의 분비를 촉진한다. Macrophages are involved in the maintenance of homeostasis in response to various host reactions such as acquired immunity as well as innate immunity, and play important roles in biological defense in the early stage of infection by producing nitric oxide (NO) and various cytokines during inflammatory reaction. Macrophage or monocytes such as RAW 264.7 have been shown to stimulate tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-1β by the stimulation of endotoxin lipopolysaccharide (LPS) 6 promotes the secretion of inflammatory mediators such as cytokines.
한편, 알레르기(Allergy)는 면역시스템의 오작동으로 보통 사람에게는 별 영향이 없는 물질이 특정 사람에게만 두드러기, 가려움, 콧물, 기침 등의 과민반응을 유발하는 질환으로서, 환경오염, 식생활과 생활습관의 서구화, 스트레스와 같은 환경인자, 유전, 및 다양한 알레르겐에 의해 유발될 수 있다. 전 세계 인구의 20~25%가 알레르기성 질환에 노출되어 있으며, 유병률이 계속적으로 증가하는 추세이다.Allergy is a disease caused by a malfunction of the immune system that causes irritation such as urticaria, itching, runny nose, and cough in a specific person. It is a disease caused by environmental pollution, westernization of diet and lifestyle , Environmental factors such as stress, genetics, and various allergens. Twenty to 25 percent of the world's population is exposed to allergic diseases, and the prevalence of this disease continues to rise.
알레르기 반응은 발현시간과 타입에 기초하여 전통적으로 4개의 부류로 나뉘는데, Ⅰ-Ⅲ형은 항체가 관여하는 체액성 면역반응(즉시형)이고, Ⅳ형은 세포가 직접 관여하는 세포성 면역반응(지연형)이다. 대부분의 알레르기 반응은 Ⅰ형으로 천식, 비염, 결막염, 식품 및 약물 알레르기, 및 아토피피부염 등이 대표적인 질환이고, 심한 경우 아나필락시스(anaphylaxis)가 유발될 수도 있다. Allergic reactions are traditionally divided into four classes based on the time and type of expression: type I-type III is a humoral immune response (immediate type) involving antibodies, type IV is a cell-mediated immune response Delay type). Most allergic reactions are type I, and are typical diseases such as asthma, rhinitis, conjunctivitis, food and drug allergy, and atopic dermatitis. In severe cases, anaphylaxis may occur.
제 I형 즉시형 과민반응은 2단계로 나뉘는데, 제1단계는 알레르겐의 체내 침입에 의하여 IgE와 IgG1의 분비를 억제하고 IgG2a의 분비를 증가시키는 IL-12 및 IFN-γ를 생산하는 Th1 세포반응과 IL-4, IL-5 및 IL-13 등을 생산하는 Th2(type2 helper T) 세포반응의 균형이 Th2 쪽으로 기울어지게 되어 Th2의 과도한 면역반응으로 IL-4, IL-13 등이 분비되고, 그 영향으로 B 세포가 생산한 IgE 특이 항체들이 비만세포(mast cell)나 호염기구(basophil)의 표면에 부착되어 알레르기 발증이 준비된 단계로써 이를 알레르겐에 감작되었다고 한다.The type I immediate-type hypersensitivity reaction is divided into two stages. In the first step, the Th1 cell reaction which produces IL-12 and IFN-γ which suppresses the secretion of IgE and IgG1 by the invasion of the allergen and increases the secretion of IgG2a And Th2 (
알레르기 발증의 제2단계는 초기반응과 후기반응으로 나뉘며, 초기반응은 알레르겐이 체내에 재침입하여 비만세포를 자극하고 탈과립 반응을 유발하며 이때 방출된 히스타민, 지질 대사물, 사이토카인 등에 의한 혈관확장 등이 일어나는 것이고, 후기반응은 해당조직에 호중구, 호산구, 대식세포, Th2 세포, 호염기구 등이 침윤하여 활성화됨으로써 염증이 유발되어 아토피피부염, 비염, 천식 등을 일으키는 것이다. 이 같은 탈과립 분비 물질 중 히스타민은 가장 잘 알려진 인자이며, 즉각형 과민반응과도 관련되어 알레르기 증상의 중요한 지표로 사용되고 있다.The second stage of the allergic manifestation is divided into an initial reaction and a late reaction. The initial reaction re-enters the body to stimulate mast cells and triggers the degranulation reaction. At this time, the vasodilation by histamine, lipid metabolites, cytokines, And late response is activated by infiltration of neutrophils, eosinophils, macrophages, Th2 cells, basophils, and the like in the tissues, thereby causing inflammation and causing atopic dermatitis, rhinitis and asthma. Among these degranulation secretions, histamine is the most well-known factor and is also used as an important indicator of allergic symptoms in relation to immediate hypersensitivity reaction.
알레르기 치료제는 21세기에 주류를 이루며 활발히 연구가 지속되고 있어 약 26조원의 세계시장이 형성되어 있으며, 건강기능성 식품 시장은 6.5조원으로 약 10%대로 성장할 것으로 예상되고 있다. 미국에서는 약 5,000만 명이 다양한 알레르기 질환을 보유하고 있으며 약 52억불의 의약품 시장이 형성되어 있다. 국내의 경우에는 알레르기 질환 치료제 시장이 4,400억 원, 건강기능성 식품시장은 1,450억 원 규모로 지속적으로 증가하고 있다. Allergy remedies have been the mainstream in the 21st century and have been actively researched. The global market of about 26 trillion won has been formed, and the health functional food market is expected to grow to about 10% by 6.5 trillion won. Approximately 50 million people in the US have diverse allergic diseases and about $ 5.2 billion in the drug market. In Korea, the market for anti-allergic drugs is 440 billion won, while the market for health functional food is steadily increasing to 145 billion won.
그러나 현재 알레르기의 치료를 위한 대부분의 약물들은 알레르기 기전의 마지막 단계에서 분비되는 히스타민의 분비를 억제하거나, 알레르기에 의한 증상을 치료하는데 치중되어 있으며 확실한 효과를 보이는 치료제가 거의 없다. 알레르기 질환의 치료는 장기간 이루어질 수 있는데, 대부분 탁월한 치료효과를 보이는 약물들은 스테로이드제로써 아토피피부염, 알레르기 비염, 천식 등에 널리 사용되고 있으나, 장기간 사용은 심각한 부작용을 초래할 수 있다(알레르기 질환의 새로운 치료 타겟 발굴 및 응용. 보건복지부, 2010). 항히스타민제 또한 증상들이 완화되는 것처럼 느끼게 되나, 장기간의 사용은 우울증, 집중력 장애, 무기력증, 졸림, 간장장애 등의 부작용을 유발하고 사용을 중단하면 알레르기 질환이 재발하는 문제점이 있다. 더욱이, 알레르기 질환 특히, 아토피피부염은 소아, 청소년 환자들이 대부분이므로 독성과 부작용이 없는 안전성이 확보된 치료제의 개발이 매우 중요하며, 이러한 한계점을 극복하고자 하는 연구가 활발하게 이루어지고 있으나, 치료제 개발이 쉽지 않은 실정이다. 이에 따라 이러한 약물들의 복용량을 줄이고 어느 정도 대체할 수 있으며, 장기간 치료에도 부작용이 없는 안전한 기능성식품 개발의 필요성이 대두되고 있다.However, most of the drugs currently used for the treatment of allergy are focused on the suppression of the secretion of histamine secreted in the last stage of the allergy mechanism, or the treatment of the symptoms caused by allergy. Treatment of allergic diseases can be done for a long period of time. Most of the drugs with excellent therapeutic effect are steroids, which are widely used for atopic dermatitis, allergic rhinitis and asthma, but long term use can cause serious side effects And application. Ministry of Health and Welfare, 2010). Antihistamines also cause symptoms to feel alleviated, but long-term use causes side effects such as depression, concentration difficulties, lethargy, drowsiness, and hepatic disorders, and the problem of recurrence of allergic diseases is discontinued. Furthermore, since allergic diseases, especially atopic dermatitis, are mostly in children and adolescents, it is very important to develop a safe therapeutic agent free from toxicity and side effects, and researches to overcome these limitations are actively conducted. However, It is not easy. Accordingly, there is a growing need for the development of safe functional foods which can reduce the dose of these drugs and replace them to some extent, and have no side effects for long-term treatment.
본 발명은 상기와 같은 문제점을 해결하기 위해 안출된 것으로서, 본 발명자들은 알레르기와 같은 Th2 면역 반응에 의해 유발되는 질환 또는 염증성 질환의 예방 또는 치료 효과를 증진시키기 위해 예의 연구한 결과, 엘라그산 (ellagic acid)이 인터루킨-4 (IL-4), 인터루킨-6(IL-6), 및 대식세포 염증단백질-2(MIP-2) 억제 활성을 가짐을 확인하였을 뿐만 아니라, 상기 엘라그산에 효소를 처리한 경우 효소를 처리하지 않은 엘라그산에 비하여 IL-4, IL-6, 및 MIP-2 억제 활성이 현저히 증진되는 것을 확인하였는바, 이에 기초하여 본 발명을 완성하였다.Disclosure of the Invention The present invention has been conceived to solve the above-mentioned problems. The present inventors have made intensive studies to improve the preventive or therapeutic effect of a disease caused by a Th2 immune response such as an allergy or an inflammatory disease, acid has inhibitory activity against interleukin-4 (IL-4), interleukin-6 (IL-6) and macrophage inflammatory protein-2 (MIP-2) 4, IL-6, and MIP-2 in comparison with the untreated enzyme, the present inventors have completed the present invention based on this finding.
본 발명의 목적은 효소처리 엘라그산 (ellagic acid)을 유효성분으로 포함하는, Th2-매개 면역질환 또는 염증성 질환의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.An object of the present invention is to provide a pharmaceutical composition for preventing or treating a Th2-mediated immune disease or inflammatory disease, which comprises an enzyme-treated ellagic acid as an active ingredient.
본 발명의 다른 목적은 효소처리 엘라그산 (ellagic acid)을 유효성분으로 포함하는, Th2-매개 면역질환 또는 염증성 질환의 예방 또는 개선용 건강기능성 식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a health functional food composition for preventing or ameliorating a Th2-mediated immunological disease or inflammatory disease, which comprises an enzyme-treated ellagic acid as an active ingredient.
본 발명의 또 다른 목적은 효소처리 엘라그산 (ellagic acid)을 유효성분으로 포함하는, Th2-매개 면역질환 또는 염증성 질환의 예방 또는 개선용 화장료 조성물을 제공하는 것이다.Yet another object of the present invention is to provide a cosmetic composition for preventing or ameliorating a Th2-mediated immunological disease or inflammatory disease, which comprises an enzyme-treated ellagic acid as an active ingredient.
그러나 본 발명이 이루고자 하는 기술적 과제는 이상에서 언급한 과제에 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 당업자에게 명확하게 이해될 수 있을 것이다. However, the technical problem to be solved by the present invention is not limited to the above-mentioned problems, and other matters not mentioned can be clearly understood by those skilled in the art from the following description.
상기 목적을 달성하기 위하여, 본 발명은In order to achieve the above object,
효소처리 엘라그산 (ellagic acid)을 유효성분으로 포함하는, Th2-매개 면역질환 또는 염증성 질환의 예방 또는 치료용 약학적 조성물을 제공한다.There is provided a pharmaceutical composition for the prevention or treatment of a Th2-mediated immune disease or inflammatory disease, which comprises an enzyme-treated ellagic acid as an active ingredient.
본 발명의 일 구현예로, 상기 Th2-매개 면역질환은 알레르기 질환일 수 있다.In one embodiment of the present invention, the Th2-mediated immune disease may be an allergic disease.
본 발명의 다른 구현예로, 상기 조성물은 인터루킨-4 (IL-4)의 생성을 억제할 수 있다.In another embodiment of the present invention, the composition may inhibit the production of interleukin-4 (IL-4).
본 발명의 또 다른 구현예로, 상기 조성물은 대식세포 염증단백질(macrophage inflammatory protein-2, MIP-2) 또는 인터루킨-6 (IL-6)의 생성을 억제할 수 있다.In another embodiment of the present invention, the composition may inhibit the production of macrophage inflammatory protein-2 (MIP-2) or interleukin-6 (IL-6).
본 발명의 또 다른 구현예로, 상기 효소는 디에노코커스 지오써르말리스 (Deinococcus geothermalis)유래의 아밀로수크라아제 (DGAS)일 수 있다.In another embodiment of the present invention, the enzyme may be amylose sucrose (DGAS) derived from Deinococcus geothermalis.
또한, 본 발명은 효소처리 엘라그산 (ellagic acid)을 유효성분으로 포함하는, Th2-매개 면역질환 또는 염증성 질환의 예방 또는 개선용 건강기능성 식품 조성물을 제공한다.The present invention also provides a health functional food composition for preventing or ameliorating a Th2-mediated immune disease or inflammatory disease, which comprises an enzyme-treated ellagic acid as an active ingredient.
또한, 본 발명은 효소처리 엘라그산 (ellagic acid)을 유효성분으로 포함하는, Th2-매개 면역질환 또는 염증성 질환의 예방 또는 개선용 화장료 조성물을 제공한다.Further, the present invention provides a cosmetic composition for preventing or ameliorating a Th2-mediated immunological disease or inflammatory disease, which comprises an enzyme-treated ellagic acid as an active ingredient.
또한, 본 발명은 상기 조성물을 개체에 투여하는 단계를 포함하는, Th2-매개 면역질환 또는 염증성 질환의 예방 또는 치료 방법을 제공한다. The present invention also provides a method of preventing or treating a Th2-mediated immune disease or inflammatory disease, comprising the step of administering the composition to a subject.
또한, 본 발명은 상기 조성물의 Th2-매개 면역질환 또는 염증성 질환의 예방 또는 치료 용도를 제공한다.The present invention also provides the use of the composition for the prevention or treatment of a Th2-mediated immune or inflammatory disease.
본 발명에 따른 조성물은 효소처리 엘라그산 (ellagic acid)을 유효성분으로 포함함으로써, 엘라그산의 항알레르기 효과 및 항염증 효과를 향상시킬 수 있음을 확인하였다. 구체적으로, 본 발명자들은 OVA로 면역시킨 마우스의 비장세포에 효소처리 엘라그산을 처리한 결과, 효소를 처리하지 않은 엘라그산에 비하여 IL-4 생성 억제활성이 현저하게 증진되는 것을 확인하였으며, 대식세포에 효소처리 엘라그산을 처리한 결과, 엘라그산에 비해 MIP-2 및 IL-6 생성 억제활성이 증진되는 것을 확인하였다. 따라서, 본 발명에 따른 조성물은 Th2-매개 면역질환 또는 염증성 질환의 예방, 개선, 또는 치료를 위한 치료제, 건강기능성 식품, 및 화장품의 개발에 유용하게 이용될 수 있을 것으로 기대된다.The composition according to the present invention has improved antiallergic and anti-inflammatory effects of elastase by containing enzyme-treated ellagic acid as an active ingredient. Specifically, the inventors of the present invention found that splenocytes treated with the enzyme-treated gelatin of mice immunized with OVA significantly enhanced the inhibitory activity of IL-4 production compared to the unlabeled elastase, Treated with the enzyme-treated ellagic acid showed that the activity of inhibiting MIP-2 and IL-6 production was enhanced as compared with that of eragacillus. Accordingly, the composition according to the present invention is expected to be useful for the development of therapeutic agents, health functional foods, and cosmetics for the prevention, improvement, or treatment of Th2-mediated immune diseases or inflammatory diseases.
도 1은 본 발명에 따른 효소처리 엘라그산을 OVA로 면역시킨 마우스 비장세포에 처리하고, 72시간 동안 세포를 배양한 후 배양액으로부터 IL-4의 양을 ELISA로 측정한 결과와 세포증식율을 ratio(IL-4/MTT)로 나타낸 것이다.
도 2는 본 발명에 따른 효소처리 엘라그산을 MH-S cell line 및 RAW 264.7 cell line에 처리한 후 MIP-2의 양을 측정한 결과와 세포증식율을 ratio(MIP-2/WST)로 나타낸 것이다.
도 3은 본 발명에 따른 효소처리 엘라그산을 MH-S cell line에 처리한 후 IL-6의 양을 측정한 결과와 세포증식율을 ratio(IL-6/WST)로 나타낸 것이다.FIG. 1 is a graph showing the results of measurement of the amount of IL-4 from the culture solution after ELISA treatment according to the present invention with mouse OVA-immunized mouse spleen cells for 72 hours and ELISA and cell proliferation ratio IL-4 / MTT).
2 shows the results of measuring the amount of MIP-2 and the cell proliferation ratio (MIP-2 / WST) after treating the enzyme-treated elastase of the present invention with the MH-S cell line and the RAW 264.7 cell line .
FIG. 3 shows the results of measuring the amount of IL-6 and the cell proliferation ratio (IL-6 / WST) after treating the enzyme-treated elastase of the present invention with the MH-S cell line.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명은 효소처리 엘라그산 (ellagic acid)을 유효성분으로 포함하는, Th2-매개 면역질환 또는 염증성 질환의 예방 또는 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating a Th2-mediated immune disease or inflammatory disease, which comprises an enzyme-treated ellagic acid as an active ingredient.
본 발명에서 사용되는 용어, “예방”이란 본 발명에 따른 약학적 조성물의 투여에 의해 Th2-매개 면역질환 또는 염증성 질환을 억제시키거나 발병을 지연시키는 모든 행위를 의미한다.As used herein, the term " prophylactic " means any action that inhibits or delays the development of a Th2-mediated immune or inflammatory disease by administration of a pharmaceutical composition according to the present invention.
본 발명에서 사용되는 용어, “치료”란 본 발명에 따른 약학적 조성물의 투여에 의해 Th2-매개 면역질환 또는 염증성 질환에 대한 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다. As used herein, the term " treatment " refers to any action that improves or alters the symptoms of a Th2-mediated immune disease or inflammatory disease by the administration of the pharmaceutical composition of the present invention.
본 발명에서 사용되는 용어 효소란, 생명체 내 화학 반응의 촉매가 되는 것으로, 생체 세포가 생산하는 단백질성의 고분자 유기 촉매를 의미한다. 동물, 식물 등 모든 생물의 세포 속에는 여러 종류의 효소가 존재하며, 생명체의 화학적 반응에 관여한다. 효소는 그 화학 구조가 매우 복잡하므로 기질의 종류나 반응 형식에 따라 분류하며, 반응의 종류에 따라 가수 분해 효소(hydrolase), 전이 효소(transferase), 리아제(lyase) 및 신테타아제(synthetase), 이소메라아제(isomerase)로 분류된다. 효소는 의약품, 아밀라아제에 의한 녹말 당화의 대규모 이용, 치즈 제조, 과즙의 청정, 섬유공업, 비타민과 아미노산 등의 합성 등 다양한 용도로 이용되고 있다. 본 발명에서는 엘라그산의 활성을 증진시키기 위하여 디에노코커스 지오써르말리스 (Deinococcus geothermalis)유래의 아밀로수크라아제 (DGAS)을 사용하는 것이 바람직하나, 엘라그산의 활성을 증진시키기 위한 당전이 효소라면 제한없이 사용할 수 있다.The term enzyme as used in the present invention means a polymeric organic catalyst produced by a living body cell which becomes a catalyst for a chemical reaction in a living organism. There are various kinds of enzymes in the cells of all living things such as animals and plants, and they are involved in the chemical reaction of living things. Enzymes are very complex because their chemical structures are very complex. They are classified according to the kind of substrate and reaction type. Depending on the type of reaction, hydrolase, transferase, lyase and synthetase, It is classified as isomerase. Enzymes are used for a variety of purposes such as pharmaceuticals, large-scale use of starch saccharification by amylase, cheese production, juice purification, textile industry, synthesis of vitamins and amino acids. In the present invention, it is preferable to use amylose sucrose (DGAS) derived from Deinococcus geothermalis in order to enhance the activity of eragic acid. However, if it is a glycoprotein for promoting the activity of eragic acid Can be used without restrictions.
본 발명에서 사용되는 용어, “T세포”는 인터류킨-2(IL-2), 인터페론-γ(IFN-γ) 등을 생산하는 Th1 세포와 IL-4, IL-5, IL-13 등을 생산하는 Th2 세포로 구성된다. 이들 Thl과 Th2세포가 생산하는 사이토카인에 의해 조절되는 면역균형을 Thl/Th2 균형이라고 하며, Thl세포는 세포성 면역의 조절에 중요하고, Th2세포는 체액성 조절에 중요한 역할을 한다고 알려져 있다. 정상상태에서는 Thl의 분화에 중요한 IFN-γ를 중심으로 한 사이토카인과 Th2의 분화에 중요한 IL-4를 주로 한 사이토카인이 서로 간섭하면서 Thl/Th2 균형을 일정하게 유지하고 있다. 그러나 Thl/Th2 균형이 깨지면 다양한 면역질환을 유발할 수 있는데, Thl에 편향한 경우에는 세포성 면역이 부활하여 감염저항성이 증강하고, Th2에 편향한 경우에는 감염저항성이 감소하고, 역으로 알레르기가 증강한다.The term " T cell " used in the present invention refers to a cell that produces Th1 cells and IL-4, IL-5 and IL-13 that produce interleukin-2 (IL-2) and interferon- Th2 cells. The immune balance regulated by the cytokines produced by these Th1 and Th2 cells is called the Th1 / Th2 balance, and Th1 cells are important for the regulation of cellular immunity, and Th2 cells are known to play an important role in controlling humoral immune responses. In the normal state, the cytokine, which is important for the differentiation of Th1, is interfering with the cytokine mainly composed of IFN-γ and IL-4, which is important for differentiation of Th2, and the Thl / Th2 balance is kept constant. However, when the Th1 / Th2 balance is broken, various immune diseases can be induced. In the case of deflecting Thl, the cellular immunity is revived to increase the resistance to infection. When the Th2 is deflected, the infection resistance decreases. Conversely, do.
본 발명에서 대상으로 하는 질병인 “Th2-매개 면역질환”은 알레르겐-특히 Th2 세포의 생성 및 활성에 의한 IgE 및 비만세포가 관여하는 질환을 의미하며, 예컨대 알레르기를 포함하며, 보다 구체적으로는 아토피피부염을 포함하는 피부질환, 급성 및 만성 알레르기성 비염, 천식, 식품 알레르기 등을 포함할 수 있으나, 이에 제한되는 것은 아니다.The term " Th2-mediated immune disease ", which is a disease targeted by the present invention, refers to a disease in which IgE and mast cells are involved in the production and activity of allergens, particularly Th2 cells. Examples of such diseases include allergies, Skin diseases including dermatitis, acute and chronic allergic rhinitis, asthma, food allergies, and the like.
본 발명에서 대상으로 하는 질병인 “염증성 질환”은 대장염, 염증성 장질환, 천식, 결막염, 치주염, 골관절염, 퇴행성 관절염, 류머티스성 관절염, 비염, 중이염, 인후염, 편도염, 폐렴, 크론병, 강직성 척추염, 건염, 건초염, 제1형 당뇨병, 제2형 당뇨병, 반응성 관절염(Reactive Arthritis), 건선, 공피증, 골다공증, 아테롬성 동맥경화증, 심근염, 심내막염, 심낭염, 낭성 섬유증, 하시모토 갑상선염, 및 과민성 대장증후군으로 이루어진 군으로부터 선택된 하나 이상일 수 있으나, 이에 제한되지 않는다."Inflammatory diseases" which are the object of the present invention include inflammatory bowel disease, inflammatory bowel disease, asthma, conjunctivitis, periodontitis, osteoarthritis, degenerative arthritis, rheumatoid arthritis, rhinitis, otitis, sore throat, tonsillitis, pneumonia, Crohn's disease, And is characterized by chronic inflammatory bowel disease, chronic inflammatory bowel disease, diarrhea,
본 발명의 일실시예에서는 효소처리 엘라그산 (ellagic acid)에 대하여 Th2-매개 면역질환 또는 염증성 질환의 개선 또는 치료효과를 확인하기 위해 하기와 같은 실험을 진행하였다. In one embodiment of the present invention, the following experiment was conducted to confirm the improvement or therapeutic effect of the enzyme-treated ellagic acid on a Th2-mediated immunological disease or an inflammatory disease.
본 발명의 일실시예에서는, OVA로 면역한 마우스로부터 분리하여 배양한 비장세포에 OVA, 효소처리 엘라그산 (ellagic acid)을 다양한 농도로 처리한 후 세포를 배양한 결과, 상기 효소처리 엘라그산 (ellagic acid)의 IL-4 억제활성이 효소를 처리하지 않은 엘라그산에 비하여 현저히 증진된 것을 확인하였다(실시예 1 참조).In one embodiment of the present invention, splenocytes isolated from OVA-immunized mice were treated with various concentrations of OVA, enzyme-treated ellagic acid, and then the cells were cultured. As a result, the enzyme- ellagic acid) significantly enhanced the IL-4 inhibitory activity compared to the untreated eragic acid (see Example 1).
본 발명의 다른 실시예에서는, 대식세포(MH-S cell line, RAW 264.7 cell line)에 효소처리 엘라그산을 다양한 농도로 처리한 결과, 상기 효소처리 엘라그산의 MIP-2 및 IL-6 억제활성이 효소를 처리하지 않은 엘라그산에 비하여 현저히 증진된 것을 확인하였다(실시예 2 참조).In another embodiment of the present invention, the enzyme-treated elastase was treated at various concentrations in the macrophage (MH-S cell line, RAW 264.7 cell line), and the MIP-2 and IL- It was confirmed that the enzyme was significantly enhanced compared with the untreated enzyme (see Example 2).
따라서, 본 발명의 상기 조성물이 IL-4, MIP-2, 및 IL-6의 생성을 억제할 수 있음을 구체적으로 확인하였다.Thus, it was specifically confirmed that the composition of the present invention can inhibit the production of IL-4, MIP-2, and IL-6.
본 발명에서 사용되는 용어 “대식세포(macrophage)”는 동물 체내 모든 조직에 분포하여 면역을 담당하는 세포로, 이물질, 세균, 바이러스, 체내 노폐세포 등을 포식하고 소화하여, 그에 대항하는 면역정보를 림프구에 전달한다. 대식세포는 자연면역이나 염증반응에서 중요한 역할을 할 뿐 아니라, 획득면역반응에서도 중요한 역할을 하며, 그 대표적인 기능이 T cell에 항원을 보여주는 것이다(antigen presentation). 대식세포는 T cell에 항원을 제시할 뿐 아니라 IL-1과 같은 cytokine을 분비하여 T cell의 활성화를 촉진할 수 있다. 또한, 대식세포는 면역반응의 시작에 필요한 항원을 제시하는 기능이 외에도, 세포매개성 면역반응과 체액성 면역반응에서 면역작용을 나타내는 중요한 작용세포(effector cell)로 활동하기도 한다. T cell에 의해 활성화된 대식세포는 지연성과민반응 (delayed type hypersensitivity)에서 항원을 제거하는 기능을 하며, 대식세포는 항체가 결합되어 있는 항원을 식균작용으로 제거하는 기능을 가지고 있다.The term " macrophage " as used in the present invention refers to a cell that is distributed in all tissues of an animal body and is responsible for immunity. It predisposes and digests foreign substances, bacteria, viruses, reticulocytes and the like, To the lymphocytes. Macrophages play an important role in innate immune and inflammatory responses as well as in acquired immune responses, and its typical function is antigen presentation to T cells. Macrophages not only present antigens to T cells but also secrete cytokines such as IL-1 and promote T cell activation. In addition, macrophages also function as effector cells that exhibit immune responses in cell-mediated immune responses and humoral immune responses in addition to their ability to present antigens necessary for the initiation of an immune response. Macrophages activated by T cells function to remove antigens from delayed type hypersensitivity. Macrophages have the function of eliminating antigens bound by antibodies with phagocytosis.
본 발명에서 사용되는 용어 “MIP(macrophage inflammatory protein)”는 대식세포가 생산하는 헤파린결합성 염증성 단백질로 케모카인의 일종이며, MIP패밀리에는 C-C케모카인에 속하는 MIP-1α,β와 C-X-C케모카인에 속하는 MIP-2가 있다. The term " MIP (macrophage inflammatory protein) " used in the present invention is a heparin-binding inflammatory protein produced by macrophages and is a kind of chemokine. MIP family includes MIP-1α, β belonging to CC chemokine, and MIP- There are two.
본 발명에 따른 약학적 조성물은 효소처리 엘라그산 (ellagic acid)을 유효성분으로 포함하며, 약학적으로 허용 가능한 담체를 더 포함할 수 있다. 상기 약학적으로 허용 가능한 담체는 제제시에 통상적으로 이용되는 것으로서, 식염수, 멸균수, 링거액, 완충 식염수, 사이클로덱스트린, 덱스트로즈 용액, 말토덱스트린 용액, 글리세롤, 에탄올, 리포좀 등을 포함하지만 이에 한정되지 않으며, 필요에 따라 항산화제, 완충액 등 다른 통상의 첨가제를 더 포함할 수 있다. 또한, 희석제, 분산제, 계면활성제, 결합제, 윤활제 등을 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다. 적합한 약학적으로 허용되는 담체 및 제제화에 관해서는 레밍턴의 문헌에 개시되어 있는 방법을 이용하여 각 성분에 따라 바람직하게 제제화할 수 있다. 본 발명의 약학적 조성물은 제형에 특별한 제한은 없으나 주사제, 흡입제, 피부 외용제 등으로 제제화할 수 있다. The pharmaceutical composition according to the present invention comprises an enzyme-treated ellagic acid as an active ingredient, and may further comprise a pharmaceutically acceptable carrier. Such pharmaceutically acceptable carriers are those conventionally used in the field of application and include, but are not limited to, saline, sterile water, Ringer's solution, buffered saline, cyclodextrin, dextrose solution, maltodextrin solution, glycerol, ethanol, And may further contain other conventional additives such as antioxidants and buffers as needed. In addition, it can be formulated into injectable formulations, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like by additionally adding diluents, dispersants, surfactants, binders, lubricants and the like. Suitable pharmaceutically acceptable carriers and formulations can be suitably formulated according to the respective ingredients using the methods disclosed in Remington's reference. The pharmaceutical composition of the present invention is not particularly limited to a formulation, but may be formulated into injections, inhalants, external skin preparations, and the like.
본 발명의 약학적 조성물은 목적하는 방법에 따라 경구 투여하거나 비경구투여(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.The pharmaceutical composition of the present invention may be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically) depending on the intended method, and the dose may vary depending on the condition and the weight of the patient, The mode of administration, the route of administration, and the time, but may be appropriately selected by those skilled in the art.
본 발명의 약학적 조성물은 약학적으로 유효한 양으로 투여한다. 본 발명에 있어서 약학적으로 유효한 양은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효용량 수준은 환자의 질환 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명에 다른 약학적 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와는 순차적 또는 동시에 투여될 수 있으며, 단일 또는 다중 투여될 수 있다. 상기한 요소들을 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다.The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, a pharmaceutically effective amount means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment. The effective dose level is determined depending on the type of disease, severity, drug activity, , The time of administration, the route of administration and rate of excretion, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts. The pharmaceutical composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, sequentially or concurrently with conventional therapeutic agents, and may be administered singly or in multiple doses. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without side effects, which can be easily determined by those skilled in the art.
구체적으로 본 발명의 약학적 조성물의 유효량은 환자의 연령, 성별, 상태, 체중, 체내에 활성 성분의 흡수도, 불활성률 및 배설속도, 질병종류, 병용되는 약물에 따라 달라질 수 있으며, 일반적으로는 체중 1 ㎏ 당 0.001 내지 150 ㎎, 바람직하게는 0.01 내지 100 ㎎을 매일 또는 격일 투여하거나, 1일 1 내지 3회로 나누어 투여할 수 있다. 그러나 투여 경로, 비만의 중증도, 성별, 체중, 연령 등에 따라서 증감될 수 있으므로 상기 투여량이 어떠한 방법으로도 본 발명의 범위를 한정하는 것은 아니다.Specifically, the effective amount of the pharmaceutical composition of the present invention may vary depending on the age, sex, condition, body weight, the degree of absorption of the active ingredient in the body, the rate of inactivation and the excretion rate, the type of disease, 0.001 to 150 mg, preferably 0.01 to 100 mg per kg of body weight, may be administered daily or every other day, or one to three divided doses per day. However, the dosage may be varied depending on the route of administration, the severity of obesity, sex, weight, age, etc. Therefore, the dosage is not limited to the scope of the present invention by any means.
본 발명의 다른 양태로서, 본 발명은 효소처리 엘라그산 (ellagic acid)을 유효성분으로 포함하는, Th2-매개 면역질환 또는 염증성 질환의 예방 또는 개선용 건강기능성 식품 조성물을 제공한다. As another aspect of the present invention, the present invention provides a health functional food composition for preventing or ameliorating a Th2-mediated immune disease or inflammatory disease, which comprises an enzyme-treated ellagic acid as an active ingredient.
본 발명에서 사용되는 용어, "개선"이란 치료되는 상태와 관련된 파라미터, 예를 들면 증상의 정도를 적어도 감소시키는 모든 행위를 의미한다. 이때 상기 건강기능성 식품 조성물은 Th2-매개 면역질환 또는 염증성 질환의 개선을 위하여 해당 질환의 발병 단계 이전 또는 발병 후, 치료를 위한 약제와 동시에 또는 별개로서 사용될 수 있다.As used herein, the term "improvement" means all actions that at least reduce the degree of symptom associated with the condition being treated. Herein, the health functional food composition may be used simultaneously with or separately from the medicament for treatment before or after the onset of the disease for the improvement of the Th2-mediated immunological disease or inflammatory disease.
본 발명에서 사용되는 용어, 건강기능성 식품 조성물은 담체, 희석제, 부형제, 및 첨가제 중 하나 이상을 포함하여 정제, 환제, 산제, 과립제, 분말제, 캡슐제, 및 액제 제형으로 이루어진 군에서 선택된 하나로 제형된 것을 특징으로 한다. 본 발명의 추출물에 첨가할 수 있는 식품으로는, 각종 식품류, 분말, 과립, 정제, 캡슐, 시럽제, 음료, 껌, 차, 비타민 복합제, 건강기능성 식품류 등이 있다. 상기 본 발명에 더 포함될 수 있는 첨가제로는, 천연 탄수화물, 향미제, 영양제, 비타민, 광물(전해질), 풍미제(합성 풍미제, 천연 풍미제 등), 착색제, 충진제, 팩트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH조절제, 안정화제, 방부제, 산화 방지제, 글리세린, 알코올, 탄산화제 및 과육으로 이루어진 군으로부터 선택된 1종 이상의 성분을 사용할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토오스, 수크로오스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알코올이다. 상기 향미제로서 천연 향미제(타우마틴, 스테비아추출물 (예를 들어 레바우디오시드 A, 글리시르히진 등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 외에 본 발명에 따른 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제, 팩트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명에 다른 조성물은 천연 과일 주스 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 상기 담체, 부형제, 희석제, 및 첨가제의 구체적인 예로는 이에 한정하는 것은 아니나, 락토오스, 덱스트로즈, 수크로오스, 솔비톨, 만니톨, 에리스리톨, 전분, 아카시아 고무, 인산칼슘, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 미세결정성 셀룰로즈, 폴리비닐키롤리돈, 셀룰로즈, 폴리비닐피로리돈, 메틸셀룰로즈, 물, 설탕시럽, 메틸 하이드록시 벤조에이트, 프로필하이드록시 벤조에이트, 활석, 스테아르산 마그네슘 및 미네랄 오일로 이루어진 그룹으로부터 선택된 1종 이상이 사용되는 것이 바람직하다.The term health-functional food composition as used in the present invention includes at least one of a carrier, a diluent, an excipient, and an additive, and is formulated into one selected from the group consisting of tablets, pills, powders, granules, powders, capsules, . Examples of foods that can be added to the extract of the present invention include various foods, powders, granules, tablets, capsules, syrups, drinks, gums, tea, vitamin complexes, and health functional foods. Examples of the additive that can be further included in the present invention include natural carbohydrates, flavors, nutrients, vitamins, minerals (electrolytes), flavors (synthetic flavors, natural flavors and the like), colorants, fillers, At least one component selected from the group consisting of alginic acid and its salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, antioxidants, glycerin, alcohols, carbonating agents and fats can be used. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. As the above-mentioned flavors, natural flavors (tautatin, stevia extract (for example, rebaudioside A and glycyrrhizin) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used. The composition according to the present invention can be used in various forms such as flavorings such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants and heavies, factic acid and its salts, alginic acid and its salts, , pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages, etc. Other compositions according to the present invention may contain flesh for the production of natural fruit juices and vegetable drinks . These components may be used independently or in combination. Specific examples of the carrier, excipient, diluent, and additive include, but are not limited to, lactose, dextrose But are not limited to, sucrose, sorbitol, mannitol, erythritol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium phosphate, calcium silicate, microcrystalline cellulose, polyvinylquilolidone, cellulose, polyvinylpyrrolidone, methylcellulose, water , At least one selected from the group consisting of sugar syrup, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil is preferably used.
본 발명의 또 다른 양태로서, 본 발명은 효소처리 엘라그산 (ellagic aicd)을 유효성분으로 포함하는, Th2-매개 면역질환 또는 염증성 질환의 예방 또는 개선용 화장료 조성물을 제공한다.In another aspect of the present invention, the present invention provides a cosmetic composition for preventing or ameliorating a Th2-mediated immune disease or inflammatory disease, comprising an enzyme-treated ellagic acid (ellagic aicd) as an active ingredient.
본 발명의 상기 화장료 조성물은 효소처리 엘라그산 (ellagic aicd) 뿐만 아니라, 화장료 조성물에 통상적으로 이용되는 성분들을 포함할 수 있으며, 예컨대 항산화제, 안정화제, 용해화제, 비타민, 안료, 및 향료와 같은 통상적인 보조제, 그리고 담체를 포함할 수 있다. The cosmetic composition of the present invention may contain not only enzyme-treated ellagic acid but also components commonly used in cosmetic compositions, such as antioxidants, stabilizers, solubilizers, vitamins, pigments, A conventional adjuvant, and a carrier.
또한, 본 발명의 조성물은 효소처리 엘라그산 (ellagic aicd) 이외에, 효소처리 엘라그산 (ellagic aicd)과 반응하여 피부보호 효과를 손상시키지 않는 한도에서 종래부터 사용되어오던 유기 자외선 차단제를 혼합하여 사용할 수도 있다. 상기 유기 자외선 차단제로는 글리세릴파바, 드로메트리졸트리실록산, 드로메트리졸, 디갈로일트리올리에이트, 디소듐페닐디벤즈이미다졸테트라설포네이트, 디에틸헥실부타미도트리아존, 디에틸아미노하이드록시벤조일헥실벤조에이트, 디이에이-메톡시신나메이트, 로우손과 디하이드록시아세톤의 혼합물, 메틸렌비스-벤조트리아졸릴테트라메칠부틸페놀, 4-메틸벤질리덴캠퍼, 멘틸안트라닐레이트, 벤조페논-3(옥시벤존),벤조페논-4, 벤조페논-8(디옥시페벤존), 부틸메톡시디벤조일메탄, 비스에틸헥실옥시페놀메톡시페닐트리아진, 시녹세이트, 에틸디하이드록시프로필파바, 옥토크릴렌, 에틸헥실디메틸파바, 에틸헥실메톡시신나메이트, 에틸헥실살리실레이트, 에틸헥실트리아존, 이소아밀-p-메톡시신나메이트, 폴리실리콘-15(디메치코디에틸벤잘말로네이트), 테레프탈릴리덴디캠퍼설포닉애씨드 및 그 염류, 티이에이-살리실레이트 및 아미노벤조산(파바)으로 이루어진 군으로부터 선택된 1종 이상을 사용할 수 있다. In addition, the composition of the present invention may be used in combination with enzyme-treated ellagic acid (ellagic aicd) in combination with enzyme-treated ellagic acid (ellagic aicd) have. Examples of the organic UV blocking agent include glyceryl paraben, drometrizol trisiloxane, drometrizol, dipaloyyl triolate, disodium phenyldibenzimidazole tetrasulfonate, diethylhexylbutamidotriazone, diethylamino Hydroxybenzoylhexyl benzoate, di-methoxycinnamate, a mixture of Rawson and dihydroxyacetone, methylene bis-benzotriazolyltetramethylbutylphenol, 4-methylbenzylidene camphor, menthyl anthranylate, benzophenone (Benzophenone-4), benzophenone-8 (dioxyphenylbenzone), butylmethoxydibenzoylmethane, bisethylhexyloxyphenol methoxyphenyltriazine, synoxate, ethyl dihydroxypropylparaben, Ethylhexyldimethylpivalate, ethylhexylmethoxycinnamate, ethylhexylsalicylate, ethylhexyltriazone, isoamyl-p-methoxy cinnamate, polysilicon-15 (dimethicodimethylbenzalmate, At least one selected from the group consisting of terephthalylidene dicam peresophilic acid and its salts, thiai-salicylate and aminobenzoic acid (parabe) can be used.
본 발명의 화장료 조성물을 첨가할 수 있는 제품으로는, 예를 들어, 수렴화장수, 유연화장수, 영양화장수, 각종 크림, 에센스, 팩, 파운데이션 등과 같은 화장품류와 클렌징, 세안제, 비누, 트리트먼트, 미용액 등이 있다. 본 발명의 화장료 조성물의 구체적인 제형으로서는 스킨로션, 스킨 소프너, 스킨토너, 아스트린젠트, 로션, 밀크로션, 모이스쳐 로션, 영양로션, 마사지크림, 영양크림, 모이스쳐 크림, 핸드크림, 에센스, 영양에센스, 팩, 비누, 샴푸, 클렌징폼, 클렌징로션, 클렌징크림, 바디로션, 바디클렌저, 유액, 립스틱, 메이크업 베이스, 파운데이션, 프레스파우더, 루스파우더, 아이섀도 등의 제형을 포함한다. Examples of products to which the cosmetic composition of the present invention can be added include cosmetics such as astringent lotion, softening longevity lotion, nutrition lotion, various creams, essences, packs, foundation and the like, cleansing, cleanser, soap, . Specific formulations of the cosmetic composition of the present invention include skin lotions, skin softeners, skin toners, astringents, lotions, milk lotions, moisturizing lotions, nutritional lotions, massage creams, nutritional creams, moisturizing creams, hand creams, essences, It includes formulations such as soap, shampoo, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, latex, lipstick, makeup base, foundation, press powder, loose powder, eye shadow and the like.
본 발명의 바람직한 구현예에 따르면, 본 발명의 효소처리 엘라그산 (ellagic aicd)의 함량은 조성물 총 중량에 대하여 0.00001-30 중량%이며, 바람직하게는 0.5-20%이며, 보다 바람직하게는 1.0-10 중량%이다. 상기 효소처리 엘라그산 (ellagic aicd)의 함량이 0.00001 중량% 미만이면 자외선 흡수 효과가 크게 감소되고, 30 중량%를 초과하는 경우에는 피부 자극을 초래할 수 있으며, 제형상의 문제점이 발생할 수 있다.According to a preferred embodiment of the present invention, the content of the enzyme-treated ellagic acid (ellagic aicd) of the present invention is 0.00001-30% by weight, preferably 0.5-20%, more preferably 1.0- 10% by weight. If the content of the enzyme-treated ellagic acid (ellagic acid) is less than 0.00001% by weight, the effect of absorbing ultraviolet light is greatly reduced. If the content of the enzyme-treated ellagic acid is more than 30% by weight, skin irritation may be caused.
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시한다. 그러나 하기의 실시예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐, 하기 실시예에 의해 본 발명의 내용이 한정되는 것은 아니다.Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the following examples.
[실시예][Example]
실시예 1. 효소처리 엘라그산을 처리한 마우스 비장세포에서의 항알레르기 효과 확인Example 1. Confirmation of antiallergic effect in mouse splenocytes treated with enzyme-treated eragucan
1-1. 1-1. 에노코커스Enokokusu 지오써르말리스Geothermal Malis ( ( DeinococcusDeinococcus geothermalisgeothermal ) 유래 ) Origin 아밀로수크라아제Amylose sucrase ( ( DGASDGAS )의 효소 처리) Of enzyme treatment
본 발명에서 사용된 엘라그산은 Sigma-Aldrich에서 구입하여 사용하였으며 , 사용된 효소 에노코커스 지오써르말리스 (Deinococcus geothermalis) 유래 아밀로수크라아제 (DGAS)는 디에노코커스 지오써르말리스(Deinococcus geothermalis)유래 아밀로수크라아제(amylosucrase)의 유전자가 형질전환된 재조합 대장균(E. coli)으로부터 생산 및 정제하였다. The ellagic acid was purchased from Sigma-Aldrich used in the present invention, the enzyme used enoic Lactococcus Geo sseoreu Marlies (Deinococcus be a geothermalis) derived from amyl Klein dehydratase (DGAS) is a geo-diethoxy no Lactococcus sseoreu was produced and purified from Marlies (Deinococcus geothermalis) sucrase Kinase (recombinant Escherichia coli (E. coli transformants of the amylosucrase gene conversion)) as derived from amyl.
구체적으로, pHCEXHD 발현벡터(His tag 포함 벡터)에 디에노코커스 지오써르말리스(Deinococcus geothermalis)유래 아밀로수크라아제 유전자가 포함된 재조합 벡터 pHC-DGAS를 이용하여, pHC-DGAS로 형질전환된 대장균(E. coli) MC1061를 제조하였다. 이 후, 형질전환된 대장균을 앰피실린이 포함된 LB 액체 배지 5 ㎖에 접종하여 37℃에서 12시간 배양하고, 원심분리하여 균체를 수득하였다. Specifically, a recombinant vector pHC-DGAS containing an amylose sucrase gene derived from Deinococcus geothermalis was added to a pHCEXHD expression vector (His tag-containing vector), and E. coli transformed with pHC-DGAS ( E. coli ) MC1061. Thereafter, the transformed Escherichia coli was inoculated in 5 ml of LB liquid medium containing ampicillin, cultured at 37 캜 for 12 hours, and centrifuged to obtain cells.
한편, His-tag(히스-태그)가 결합된 재조합 단백질을 정제하기 위해, 상기 형질전환된 대장균(E. coli) MC1061를 37℃에서 15시간 배양하였다. 배양 후, 4℃ 및 4,000 rpm의 조건으로 30분 동안 원심분리를 수행하여 균체를 회수하였다. 이 후, 라이시스 버퍼(Lysis buffer) [50mM NaH2PO4, pH 7.0, 300mM NaCl, 10mM imidazole, pH 7.0]에 현탁하고, 초음파 분쇄하였다. Meanwhile, in order to purify the His-tag (His-tag) -binding recombinant protein, the transformed E. coli MC1061 was cultured at 37 ° C for 15 hours. After the incubation, the cells were recovered by performing centrifugation at 4 ° C and 4,000 rpm for 30 minutes. Thereafter, the mixture was suspended in a lysis buffer (50 mM NaH 2 PO 4 , pH 7.0, 300 mM NaCl, 10 mM imidazole, pH 7.0) and sonicated.
이 후, 상기 초음파를 이용하여 분쇄한 분쇄액을 4℃ 및 12,000 rpm의 조건으로 10분간 원심분리를 수행한 후, 상등액을 수득하였다. 상기 상등액을 Ni-NTA 친화 크로마토그래피에 주입하여, 재조합 단백질을 정제하였다. Thereafter, the pulverized liquid pulverized by using the ultrasonic wave was subjected to centrifugation for 10 minutes at 4 ° C and 12,000 rpm, and a supernatant was obtained. The supernatant was injected into Ni-NTA affinity chromatography to purify the recombinant protein.
엘라그산 10 mg에 300 mM sucrose와 상기 제조한 DGAS (1U/L)를 첨가하였다. 50 mM Tris-HCl pH 8.0 버퍼용액으로 100 mL 용량을 맞춘 후, 40℃에서 48시간 각각 반응하였다. 반응 후, 5분 동안 용액을 끓인 후 왓트만 여지를 이용하여 여과시켰다. 300 mg sucrose and DGAS (1 U / L) prepared above were added to 10 mg of eragacillus. The volume was adjusted to 100 mL with 50 mM Tris-HCl pH 8.0 buffer solution and reacted at 40 ° C for 48 hours, respectively. After the reaction, the solution was boiled for 5 minutes and then filtered using a Whatman filter paper.
1-2. OVA로 면역한 마우스 비장세포의 배양1-2. Culture of mouse splenocytes immunized with OVA
5주령된 암컷 BALB/c 마우스에 알레르기를 유발시키기 위하여, 10 ㎍의 오브알부민(ovalbumin; OVA)과 1 ㎎의 알럼(alum)을 30분간 섞어준 혼합액을 마우스 한 마리 당 100 ㎕씩 2주일 간격으로 2차례 복강투여 하였다(n=5). 면역 1주일 후 마우스를 경추탈골로 희생시키고 무균상태에서 비장을 적출한 후 1 ㎖의 기본배지 즉, 2-머캅토에탄올(2-mercaptoethanol)과 항생제가 첨가된 RPMI1640 배지가 담긴 작은 페트리디쉬에 옮겨 아이스 위에 보관하였다. 이후 상기 비장을 메쉬를 이용하여 단세포화 시키고 5 ㎖의 기본배지로 2회 세척한 후 1500 rpm에서 5분 동안 원심분리 하였다. 상층액을 제거한 후 1 ㎖의 RBC(red blood cell) lysing buffer(SIGMA R7757)를 첨가하여 현탁하고 3분 동안 아이스 위에서 반응시킨 후 10 ㎖의 기본배지를 더 첨가하고 재현탁한 다음 1500 rpm에서 5분 동안 원심분리를 2회 실시하였다.In order to induce allergy to female BALB / c mice at 5 weeks of age, 10 μg of ovalbumin (OVA) and 1 mg of alum were mixed for 30 minutes, and 100 μl of each mouse was injected every 2 weeks (N = 5) twice a week. One week after the immunization, the mice were sacrificed by cervical disassembly, and the spleen was removed from the aseptic state. Then, the spleen was transferred to a small petri dish containing 1 ml of the basic medium, i.e., 2-mercaptoethanol and RPMI1640 medium supplemented with antibiotics And stored on ice. The spleen was then single-celled using a mesh, washed twice with 5 ml of basal medium, and then centrifuged at 1500 rpm for 5 minutes. After removing the supernatant, 1 ml of RBC (red blood cell) lysing buffer (SIGMA R7757) was added and incubated for 3 minutes on ice. 10 ml of basal medium was further added, ≪ / RTI > centrifugation twice.
한편, 96웰 플레이트에 항원인 OVA를 100 ㎍/㎖의 농도로 처리하고, 상기 실시예 1-1의 방법에 따라 제조한 DGAS가 처리된 엘라그산 및 DGAS를 처리하지 않은 엘라그산 각각을 2.5, 및 5.0 ㎍/㎖의 농도로 첨가하였으며, 상기 방법으로 배양한 마우스의 비장세포를 5 × 106 cells/well로 처리하였다. 이 후, 37 ℃의 CO2 배양기에서 72시간 동안 배양한 후 세포 배양액을 회수하였다.On the other hand, the 96-well plate was treated with OVA as an antigen at a concentration of 100 μg / ml, and each of the DGAS-treated and DGAS-untreated eragic acid prepared in Example 1-1 was diluted 2.5, And 5.0 [mu] g / ml, and the spleen cells of the mouse cultured by the above method were treated at 5 x 10 < 6 > cells / well. Thereafter, the cells were cultured in a CO 2 incubator at 37 ° C for 72 hours, and the cell culture medium was recovered.
1-3. ELISA를 이용한 비장세포 배양액의 사이토카인 분석 결과1-3. Cytokine analysis of spleen cell cultures using ELISA
상기 실시예 1-2의 방법에 따라 회수한 마우스 비장세포의 배양액으로부터 IL-4 사이토카인의 양을 측정하기 위해, IL-4 BD OptEIATM MOUSE ELISA(enzyme-linked immunosorbent assay) kit를 이용하여 실험을 수행하였다. In order to measure the amount of IL-4 cytokine from the culture medium of the mouse spleen cells recovered according to the method of Example 1-2, an experiment using an IL-4 BD OptEIATM MOUSE ELISA kit (enzyme-linked immunosorbent assay) Respectively.
구체적으로, 96웰 플레이트에 캡쳐 항체(capture antibody)를 첨가하고 4℃에서 하룻밤 동안 반응시켜 플레이트를 항체로 코팅시키고, washing buffer(phosphate buffered saline with Tween20; PBST)로 세척한 후 assay diluent(10% FBS in PBS)를 각 웰에 넣고 상온에서 1시간 동안 반응시켜 블로킹(blocking) 과정을 수행하였다. 다음으로 표준용액(standard solution)과 상기 실시예 1-2의 방법을 통해 회수한 마우스 비장세포의 배양액을 100 ㎕씩 상기 각 웰에 분주한 후 상온에서 2시간 동안 반응시켰다. 반응 후 IL-4를 검출할 수 있는 IL-4 특이적 1차 항체와 스트렙타비딘-홀스래디쉬 퍼옥시다제(streptoavidin-HRP)가 접합된 2차 항체를 각 웰에 100 ㎕씩 분주한 후 상온에서 1시간 동안 반응시켰다. 이후 100 ㎕의 기질용액(0.01% TMB in phosphate-citrate buffer)을 첨가하고 상온에서 30분 동안 발색시킨 다음, 2 M의 H2SO4를 각 웰에 50 ㎕씩 넣어 발색반응을 중지시킨 후 450 nm에서 micro plate reader로 흡광도를 측정하였다.Specifically, a capture antibody was added to a 96-well plate and reacted overnight at 4 ° C. The plate was coated with an antibody, washed with a washing buffer (phosphate buffered saline with Tween 20; PBST), and diluted with assay diluent (10% FBS in PBS) was added to each well and reacted at room temperature for 1 hour to perform a blocking process. Next, 100 μl of the standard solution and the culture solution of mouse spleen cells recovered through the method of Example 1-2 were dispensed into the wells, and reacted at room temperature for 2 hours. After the reaction, 100 쨉 l of the secondary antibody conjugated with the IL-4 specific primary antibody capable of detecting IL-4 and streptavidin-Horseradish peroxidase (HRP) was dispensed into each well The reaction was allowed to proceed at room temperature for 1 hour. Then, 100 μl of a substrate solution (0.01% TMB in phosphate-citrate buffer) was added and developed at room temperature for 30 minutes. Then, 50 μl of 2 M H 2 SO 4 was added to each well to stop the color reaction. The absorbance was measured with a microplate reader at.
또한, 세포증식율을 측정하기 위해서 MTT assay를 수행하였다. 구체적으로, 상기 실시예 1의 방법에 따라 배양액을 회수한 후 비장세포에 2 ㎎/㎖의 농도로 PBS에 희석한 3-(4,5-diethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT) 시약 20 ㎕를 처리하였다. 4시간 후 10% SDS 용액 100 ㎕를 첨가하고 하룻밤 방치한 후 micro plate reader를 이용하여 595 nm에서 흡광도를 측정하였다.In addition, MTT assay was performed to measure cell proliferation rate. Specifically, after recovering the culture solution according to the method of Example 1, the cells were treated with 3- (4,5-diethyl thiazol-2-yl) -2,5-diphenyl 20 μl of tetrazolium bromide (MTT) reagent was treated. After 4 hours, 100 μl of 10% SDS solution was added and allowed to stand overnight. Absorbance was measured at 595 nm using a microplate reader.
그 결과, 비장세포에 OVA만 처리한 경우 알레르기 면역반응을 유도하기 위해 Th2 세포가 분비하는 사이토카인인 IL-4의 양이 현저히 증가하는 것을 확인하였으며, 효소를 처리하지 않은 엘라그산을 처리한 경우 IL-4의 양이 감소되긴 하였으나, DGAS 효소 처리한 엘라그산의 경우 효소를 처리하지 않은 엘라그산을 처리한 경우보다 IL-4의 양이 현저히 감소되는 것을 확인하였다. 이 결과는 도 1에 나타낸 바와 같이, IL-4/MTT ratio 값으로 표시되었다.As a result, it was confirmed that the amount of IL-4, which is a cytokine secreted by Th2 cells, was significantly increased in order to induce an allergic immune response when OVA alone was administered to spleen cells. In the case of treatment with the enzyme- Although the amount of IL-4 was decreased, it was confirmed that the amount of IL-4 was significantly reduced in the case of the DGAS enzyme-treated elagic acid than in the case of treatment with the enzyme-untreated elagic acid. The results are shown in Figure 1 as the IL-4 / MTT ratio value.
실시예Example 2. 효소처리 2. Enzyme treatment 엘라그산을ElaGrass 처리한 대식세포(macrophage)에서의 항염증 효과 확인 Identification of anti-inflammatory effects in treated macrophages
2-1. 효소 처리 및 cell viability 측정2-1. Enzyme treatment and cell viability measurement
Dish에 존재하는 배지를 모두 제거한 후, DPBS(Dulbecco's phosphate-buffered saline) 5ml로 2회 세척하고, DPBS를 모두 제거한 다음, MH-S cell line, RAW 264.7 cell line 배지 10ml를 dish에 분주하고, cell scrapper를 이용하여 세포를 긁어내었다. 이를 15ml tube에 옮긴 다음, 1000rpm으로 24℃에서 10분동안 원심분리한 후, tube에서 상층액을 제거하고 배지를 1ml 분주하였다. 이후 cell counter ADAM을 이용하여 cell count를 진행하였다.After removing all of the media in Dish, the cells were washed twice with 5 ml of DPBS (Dulbecco's phosphate-buffered saline), and DPBS was removed. 10 ml of the MH-S cell line and RAW 264.7 cell line medium were dispensed into the dish, The cells were scraped off using a scrapper. This was transferred to a 15 ml tube, centrifuged at 1000 rpm at 24 ° C for 10 minutes, the supernatant was removed from the tube, and 1 ml of the medium was dispensed. Then cell count was performed using cell counter ADAM.
MH-S cell line, RAW 264.7 cell line을 2×10/ml로 희석시킨 후, cell culture 96 well plate(SPL, cat. 30096)에 250μl 씩 분주하고 24시간 동안 배양하였다.MH-S cell line and RAW 264.7 cell line were diluted to 2 × 10 6 / ml, and 250 μl of the cells were added to a 96-well culture plate (SPL, cat.
그 후, LPS 100ng/ml 농도로 MH-S cell line, RAW 264.7 cell line 배지에 희석하고 이 배지에 상기 실시예 1-1의 방법에 따라 제조한 DGAS가 처리된 엘라그산 및 DGAS를 처리하지 않은 엘라그산 각각을 2.5, 및 5.0 ㎍/㎖의 농도로 희석하여 각 알맞은 well에 250μl씩 분주하고 24시간 동안 배양하였다.Thereafter, the cells were diluted with an MH-S cell line and RAW 264.7 cell line medium at a concentration of 100 ng / ml of LPS, and the DGAS-treated elastase and DGAS prepared according to the method of Example 1-1 Eulagic acid was diluted to a concentration of 2.5 and 5.0 μg / ml, and 250 μl of each was diluted into appropriate wells and cultured for 24 hours.
상기와 같이 24시간 동안 배양한 후 96 well에 존재하는 상층액을 사이토카인 측정을 위해 따로 걷어내고, MH-S cell line 배지, RAW 264.7 cell line 배지 및 cellvia 용액을 각각 10:1 비율로 혼합하여 200μl씩 분주하였다.After culturing for 24 hours, the supernatant in 96 wells was separately removed for cytokine determination, and the MH-S cell line medium, RAW 264.7 cell line medium and cellvia solution were mixed at a ratio of 10: 1 Respectively.
20분 후, 450nm 조건에서 흡광도를 측정하여 cell viability를 계산하였다.After 20 minutes, absorbance was measured at 450 nm to calculate cell viability.
2-2. 대식세포 상층액을 이용한 MIP-2 측정 2-2. MIP-2 measurement using macrophage supernatant
실험 전날 capture antibody를 PBS에 알맞은 농도로 희석하여 96 well immune plate (SPL)에 well당 100㎕씩 분주하여 overnight하고, wash 기계를 이용하여 well 당 350㎕씩 3번 세척 후 남아있는 용액을 털어낸 후, reagent diluent를 well 당 300㎕씩 처리하고 상온에서 1시간 동안 배양하였다. 1시간 후, 2번의 wash과정을 진행하고, reagent diluent를 이용하여 상기 실시예 1-1의 방법에 따라 제조한 DGAS가 처리된 엘라그산 및 DGAS를 처리하지 않은 엘라그산을 적절한 농도로 희석하여, well당 100㎕씩 처리 후 상온에서 2시간 동안 배양하였다. 2시간 후, 2번의 wash 과정을 진행하고, reagent diluent를 이용하여 detection antibody를 적절한 농도로 희석하여, well 당 100㎕씩 처리 후 상온에서 2시간 동안 배양하였다. 2시간 후, 2번의 wash 과정을 진행하고, reagent diluent를 이용하여 Streptavidin-HRP를 적절한 농도로 희석하여, well 당 100㎕씩 처리 후 상온에서 20분 동안 배양하였다. 2시간 후, 2번의 wash 과정을 진행하고, substrate solution을 well 당 100㎕씩 처리 후 빛에 노출시키지 않고 상온에서 20분 동안 배양하였다. 20분 후, stop solution을 well 당 50㎕씩 처리 후 용액이 잘 섞이도록 부드럽게 plate를 두드려주고, microplate reader를 이용하여 450nm에서 흡광도를 측정하였다. On the day before the experiment, the capture antibody was diluted to the appropriate concentration in PBS, and 100 ㎕ per well was dispensed per well in a 96-well immune plate (SPL). After washing three times with 350 ㎕ of each well using a washing machine, Subsequently, 300 μl of the reagent diluent was treated per well and cultured at room temperature for 1 hour. After 1 hour, two wash steps were carried out. Elaginic acid treated with DGAS and unlabeled elagic acid prepared according to the method of Example 1-1 were diluted to an appropriate concentration using a reagent diluent, 100 ㎕ per well was added and incubated at room temperature for 2 hours. After 2 hours, two washing steps were carried out. The detection antibody was diluted to an appropriate concentration using a reagent diluent, treated with 100 μl per well, and incubated at room temperature for 2 hours. After 2 hours, two wash steps were carried out. Streptavidin-HRP was diluted to an appropriate concentration using a reagent diluent, treated with 100 μl per well, and incubated at room temperature for 20 minutes. Two hours later, two wash steps were carried out. The substrate solution was treated with 100 μl per well, followed by incubation at room temperature for 20 minutes without exposure to light. After 20 minutes, the stop solution was treated with 50 μl per well. The plate was patched gently so that the solution was well mixed, and the absorbance was measured at 450 nm using a microplate reader.
그 결과, MH-S cell line에 LPS만 처리한 경우 MIP-2의 양이 현저히 증가하는 것을 확인하였으며, 효소를 처리하지 않은 엘라그산 2.5㎍/㎖를 처리한 경우 및 DGAS 효소 처리한 엘라그산 2.5㎍/㎖를 처리한 경우 모두 MIP-2의 양이 감소되었으며, DGAS 효소 처리한 엘라그산의 경우 효소를 처리하지 않은 엘라그산을 처리한 경우보다 MIP-2의 양이 약간 더 감소되는 것을 확인하였다. As a result, it was confirmed that the amount of MIP-2 was significantly increased when LPS alone was administered to the MH-S cell line. When 2.5 μg / ml of the enzyme-untreated elagantic acid was treated and when the DGAS enzyme- Ug / ml, the amount of MIP-2 was decreased, and the amount of MIP-2 was slightly decreased in the case of elagic acid treated with DGAS enzyme than in the case of treatment with no enzyme-treated elagic acid .
또한, RAW 264.7 cell line에서는 효소를 처리하지 않은 엘라그산 5㎍/㎖를 처리한 경우는 LPS만 처리한 경우에 비해 MIP2의 양이 감소되지 않았으나, DGAS 효소 처리한 엘라그산 5㎍/㎖를 처리한 경우 MIP-2의 양이 감소되는 것을 확인하였다. In the RAW 264.7 cell line, the amount of MIP2 was not decreased in the case of treatment with 5 g / ml of the enzyme-untreated elagantic acid, but the amount of 5 g / ml of DGAS enzyme-treated elagant was treated The amount of MIP-2 was decreased.
상기 MH-S cell line 및 RAW 264.7 cell line에서의 결과는 도 2에 나타내었으며, MIP-2/WST ratio 값으로 표시되었다.The results for the MH-S cell line and the RAW 264.7 cell line are shown in FIG. 2 and are shown as MIP-2 / WST ratio values.
2-3. 대식세포 상층액을 이용한 IL-6 측정2-3. Measurement of IL-6 using macrophage supernatant
실험 전날 capture antibody를 PBS에 알맞은 농도로 희석하여 96 well immune plate (SPL)에 well당 100㎕씩 분주하여 4℃에서 overnight하고, wash 기계를 이용하여 well 당 300㎕씩 3번 세척 후 남아있는 용액을 털어낸 후, assay diluent를 well 당 300㎕씩 처리하고 상온에서 1시간 동안 배양하였다. 이후 wash 기계를 이용하여 well 당 300㎕씩 5번 세척 후 남아있는 용액을 털어내고 assay diluent를 이용하여 상기 실시예 1-1의 방법에 따라 제조한 DGAS가 처리된 엘라그산 및 DGAS를 처리하지 않은 엘라그산을 적절한 농도로 희석하여, well당 100㎕씩 처리 후 상온에서 2시간 동안 배양하였다. 그 후 wash 기계를 이용하여 well 당 300㎕씩 7번 세척 후 남아있는 용액을 털어내고, assay diluent를 이용하여 working detector를 적절한 농도로 희석하여, well 당 100㎕씩 처리 후 상온에서 1시간 동안 배양하였다. 그 다음 substrate solution을 well 당 100㎕씩 처리 후 빛에 노출시키지 않고 상온에서 30분 동안 배양하고 30분 후, stop solution을 well 당 50㎕씩 처리하고 용액이 잘 섞이도록 부드럽게 plate를 두드려주었다. 그 후 microplate reader를 이용하여 450nm에서 흡광도를 측정하였다.On the day before the experiment, dilute the capture antibody to the appropriate concentration in PBS, dispense 100 μl per well in a 96-well immune plate (SPL), overnight at 4 ° C, wash 3 times 300 μl per well using a washing machine, , The assay diluent was treated with 300 μl per well and cultured at room temperature for 1 hour. Then, the remaining solution was washed 5 times with 300 μl per well using a washing machine, and the remaining solution was bled off. Using the assay diluent, the DGAS-treated elastase and DGAS prepared according to the method of Example 1-1 were not treated Elagic acid was diluted to an appropriate concentration, treated with 100 μl per well, and cultured at room temperature for 2 hours. After washing with 300 μL / well of the wash machine, the remaining solution was blotted off. The working detector was diluted to an appropriate concentration using an assay diluent, treated with 100 μL per well, incubated at room temperature for 1 hour Respectively. Subsequently, the substrate solution was treated with 100 μl per well, followed by incubation at room temperature for 30 minutes without exposing to light. After 30 minutes, the stop solution was treated with 50 μl per well, and the plate was gently patted so that the solution was well mixed. The absorbance was then measured at 450 nm using a microplate reader.
그 결과, MH-S cell line에 LPS만 처리한 경우 IL-6의 양이 현저히 증가하는 것을 확인하였으며, 효소를 처리하지 않은 엘라그산 2.5 및 5㎍/㎖를 처리한 경우 및 DGAS 효소 처리한 엘라그산 2.5 및 5㎍/㎖를 처리한 경우 모두 IL-6의 양이 감소되었으나, DGAS 효소 처리한 엘라그산의 경우 효소를 처리하지 않은 엘라그산을 처리한 경우보다 IL-6의 양이 현저하게 감소되는 것을 확인하였다.As a result, it was confirmed that the amount of IL-6 was significantly increased when LPS alone was administered to the MH-S cell line. When the enzyme-treated unlabeled elagance 2.5 and 5 μg / ml were treated and the DGAS enzyme- The amount of IL-6 was decreased in all of the treatment groups of 2.5 and 5 μg / ml, but the amount of IL-6 was significantly decreased in the case of the DGAS enzyme-treated elagic acid than in the untreated enzyme-treated elagic acid .
상기 MH-S cell line에서의 결과는 도 3에 나타내었으며, IL-6/WST ratio 값으로 표시되었다.The results in the MH-S cell line are shown in FIG. 3 and are shown as the IL-6 / WST ratio values.
전술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것 이며 한정적이 아닌 것으로 이해해야만 한다.It will be understood by those skilled in the art that the foregoing description of the present invention is for illustrative purposes only and that those of ordinary skill in the art can readily understand that various changes and modifications may be made without departing from the spirit or essential characteristics of the present invention. will be. It is therefore to be understood that the embodiments described above are illustrative in all aspects and not restrictive.
Claims (15)
A pharmaceutical composition for the prophylaxis or treatment of a Th2-mediated immune disease or inflammatory disease, comprising an enzyme-treated ellagic acid as an active ingredient.
The pharmaceutical composition according to claim 1, wherein the Th2-mediated immune disease is an allergic disease.
The pharmaceutical composition according to claim 1, wherein said composition inhibits the production of interleukin-4 (IL-4).
The method according to claim 1, wherein the composition inhibits the production of macrophage inflammatory protein-2 (MIP-2) or interleukin-6 (IL-6) A pharmaceutical composition for preventing or treating diseases.
The method of claim 1, wherein the enzyme is selected from the group consisting of Deinococcus A medicinal composition for the prevention or treatment of a Th2-mediated immune disease or inflammatory disease, characterized in that it is an amylose sucrose derived from geothermal origin.
A health-functional food composition for preventing or ameliorating a Th2-mediated immunological disease or inflammatory disease, which comprises an enzyme-treated ellagic acid as an active ingredient.
The health functional food composition according to claim 6, wherein the Th2-mediated immune disease is an allergic disease.
The health functional food composition according to claim 6, wherein the composition inhibits the production of interleukin-4 (IL-4).
7. The method according to claim 6, wherein the composition inhibits the production of macrophage inflammatory protein-2 (MIP-2) or interleukin-6 (IL-6) A health functional food composition for preventing or ameliorating a disease.
The method of claim 6, wherein the enzyme is selected from the group consisting of Deinococcus A medicament for preventing or ameliorating a Th2-mediated immune disease or inflammatory disease, characterized in that it is an amylose sucrose derived from geothermalis .
A cosmetic composition for preventing or ameliorating a Th2-mediated immunological disease or inflammatory disease, comprising an enzyme-treated ellagic acid as an active ingredient.
12. The cosmetic composition according to claim 11, wherein the Th2-mediated immune disease is an allergic disease.
12. The cosmetic composition according to claim 11, wherein the composition inhibits the production of interleukin-4 (IL-4).
12. The method of claim 11, wherein the composition inhibits the production of macrophage inflammatory protein-2 (MIP-2) or interleukin-6 (IL-6) A cosmetic composition for preventing or improving disease.
12. The method of claim 11, wherein the enzyme is selected from the group consisting of Deinococcus A medicinal composition for preventing or ameliorating a Th2-mediated immunological disease or an inflammatory disease, characterized in that it is amylosucrase derived from geothermalis .
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Biosci. Biotechnol. Biochem., Vol., 77, No. 4, pp. 810-813 (2013)* * |
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